MDedge Rheumatology

TOPLINE:

Pooled data from 9225 adults with psoriasis (PsO), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) showed no new safety signals with extended exposure to ixekizumab (Taltz).

METHODOLOGY:

• Researchers combined patient data from 25 randomized, controlled trials of the safety and effectiveness of at least one dose of ixekizumab in adults with PsO (n = 6892), PsA (n = 1401), and axSpA (n = 932).
• The study population included patients with a mean age of approximately 43-49 years; at least 49% were male and at least 74% were White across the three conditions.
• Patients’ median duration of ixekizumab exposure was 1.3 years for PsO, 1.4 years for PsA, and 2.7 years for axSpA, with data up to 6 years for PsO and up to 3 years for PsA and axSpA.
• The primary outcomes were exposure-adjusted incidence rates per 100 patient-years overall and at successive year intervals for treatment-emergent adverse events, serious adverse events, and selected adverse events of interest.

TAKEAWAY:

• The incidence rate per 100 person-years for any treatment-emergent adverse event was 32.5 for PsO, 50.3 for PsA, and 38.0 for axSpA; these did not increase with lengthier exposure.
• The incidence rates for serious adverse events for patients with PsO, PsA, or axSpA were 5.4, 6.0, and 4.8 per 100 person-years, respectively.
• A total of 45 deaths were reported across the studies, including 36 in patients with PsO, six with PsA, and three with axSpA.
• Infections were the most common treatment-emergent adverse events across all patient groups, reported in patients at rates of 62.5% with PsO, 52.4% with PsA, and 57.9% with axSpA; incidence of infections did not increase over time.

IN PRACTICE:

“These final, end-of-study program results surrounding the long-term use of [ixekizumab] in patients with PsO, PsA, and axSpA should serve as an important point of reference for physicians considering [ixekizumab],” the researchers wrote.

SOURCE:

The lead author on the study was Atul Deodhar, MD, of Oregon Health & Science University, Portland. The study was published online on February 12 in Arthritis Research & Therapy.

LIMITATIONS:

Study limitations included the small sample sizes and short treatment durations in some studies, the primarily White study population, the inability to stratify risk, the lack of a long-term comparator, and potential survivor bias.

DISCLOSURES:

The studies in the review were supported by Eli Lilly. Lead author Dr. Deodhar disclosed an honorarium and serving on advisory boards at AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, as well as research grants from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, MoonLake, Novartis, Pfizer, and UCB.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Pooled data from 9225 adults with psoriasis (PsO), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) showed no new safety signals with extended exposure to ixekizumab (Taltz).

METHODOLOGY:

• Researchers combined patient data from 25 randomized, controlled trials of the safety and effectiveness of at least one dose of ixekizumab in adults with PsO (n = 6892), PsA (n = 1401), and axSpA (n = 932).
• The study population included patients with a mean age of approximately 43-49 years; at least 49% were male and at least 74% were White across the three conditions.
• Patients’ median duration of ixekizumab exposure was 1.3 years for PsO, 1.4 years for PsA, and 2.7 years for axSpA, with data up to 6 years for PsO and up to 3 years for PsA and axSpA.
• The primary outcomes were exposure-adjusted incidence rates per 100 patient-years overall and at successive year intervals for treatment-emergent adverse events, serious adverse events, and selected adverse events of interest.

TAKEAWAY:

• The incidence rate per 100 person-years for any treatment-emergent adverse event was 32.5 for PsO, 50.3 for PsA, and 38.0 for axSpA; these did not increase with lengthier exposure.
• The incidence rates for serious adverse events for patients with PsO, PsA, or axSpA were 5.4, 6.0, and 4.8 per 100 person-years, respectively.
• A total of 45 deaths were reported across the studies, including 36 in patients with PsO, six with PsA, and three with axSpA.
• Infections were the most common treatment-emergent adverse events across all patient groups, reported in patients at rates of 62.5% with PsO, 52.4% with PsA, and 57.9% with axSpA; incidence of infections did not increase over time.

IN PRACTICE:

“These final, end-of-study program results surrounding the long-term use of [ixekizumab] in patients with PsO, PsA, and axSpA should serve as an important point of reference for physicians considering [ixekizumab],” the researchers wrote.

SOURCE:

The lead author on the study was Atul Deodhar, MD, of Oregon Health & Science University, Portland. The study was published online on February 12 in Arthritis Research & Therapy.

LIMITATIONS:

Study limitations included the small sample sizes and short treatment durations in some studies, the primarily White study population, the inability to stratify risk, the lack of a long-term comparator, and potential survivor bias.

DISCLOSURES:

The studies in the review were supported by Eli Lilly. Lead author Dr. Deodhar disclosed an honorarium and serving on advisory boards at AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, as well as research grants from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, MoonLake, Novartis, Pfizer, and UCB.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Pooled data from 9225 adults with psoriasis (PsO), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) showed no new safety signals with extended exposure to ixekizumab (Taltz).

METHODOLOGY:

• Researchers combined patient data from 25 randomized, controlled trials of the safety and effectiveness of at least one dose of ixekizumab in adults with PsO (n = 6892), PsA (n = 1401), and axSpA (n = 932).
• The study population included patients with a mean age of approximately 43-49 years; at least 49% were male and at least 74% were White across the three conditions.
• Patients’ median duration of ixekizumab exposure was 1.3 years for PsO, 1.4 years for PsA, and 2.7 years for axSpA, with data up to 6 years for PsO and up to 3 years for PsA and axSpA.
• The primary outcomes were exposure-adjusted incidence rates per 100 patient-years overall and at successive year intervals for treatment-emergent adverse events, serious adverse events, and selected adverse events of interest.

TAKEAWAY:

• The incidence rate per 100 person-years for any treatment-emergent adverse event was 32.5 for PsO, 50.3 for PsA, and 38.0 for axSpA; these did not increase with lengthier exposure.
• The incidence rates for serious adverse events for patients with PsO, PsA, or axSpA were 5.4, 6.0, and 4.8 per 100 person-years, respectively.
• A total of 45 deaths were reported across the studies, including 36 in patients with PsO, six with PsA, and three with axSpA.
• Infections were the most common treatment-emergent adverse events across all patient groups, reported in patients at rates of 62.5% with PsO, 52.4% with PsA, and 57.9% with axSpA; incidence of infections did not increase over time.

IN PRACTICE:

“These final, end-of-study program results surrounding the long-term use of [ixekizumab] in patients with PsO, PsA, and axSpA should serve as an important point of reference for physicians considering [ixekizumab],” the researchers wrote.

SOURCE:

The lead author on the study was Atul Deodhar, MD, of Oregon Health & Science University, Portland. The study was published online on February 12 in Arthritis Research & Therapy.

LIMITATIONS:

Study limitations included the small sample sizes and short treatment durations in some studies, the primarily White study population, the inability to stratify risk, the lack of a long-term comparator, and potential survivor bias.

DISCLOSURES:

The studies in the review were supported by Eli Lilly. Lead author Dr. Deodhar disclosed an honorarium and serving on advisory boards at AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, as well as research grants from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, MoonLake, Novartis, Pfizer, and UCB.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Eosinopenia and low ratio between eosinophil count (EC) and neutrophil count (NC) are potential indicators of infection for patients with inflammatory disease who are treated with tocilizumab.

METHODOLOGY:

• The researchers reviewed data from 163 patients treated for an inflammatory disease (mostly rheumatoid arthritis) with tocilizumab at a single center between 2009 and 2020.
• The study population included 41 patients with unscheduled hospitalizations for suspected infections. Patients’ median age was 59 years, and 83% were female.
• The researchers assessed the association in tocilizumab-treated patients between infections and eosinopenia (defined as EC < 0.05 g/L) and a low ratio between EC and NC, defined as EC/NC × 1000 < 11.8.

TAKEAWAY:

• Infectious diseases were diagnosed in 20 of the hospitalized patients (49%); the most common diseases were pneumonia (30%), joint or bone infections (25%), and gastrointestinal tract infections (15%).
• The median absolute EC at hospital admission was significantly lower for patients with infections than for those without infections (0.06 g/L vs 0.20 g/L).
• The median EC/NC × 1000 ratios were significantly lower in infected patients vs noninfected patients (6.54 vs 48.50).
• No differences appeared between patients with and without infections in age, sex, type of inflammatory disease, and steroid treatment.

IN PRACTICE:

“This original study suggests that all those easily available parameters should be used to maximize [sensitivity] in the screening of infection in patients undergoing treatment with IL-6 pathway antagonists,” the researchers wrote.

SOURCE:

The lead author on the study was Audrey Glatre, MD, of University Hospital Centre Reims, France. The study was published online in RMD Open on February 9.

LIMITATIONS:

The retrospective, observational design; relatively small study population; and use of data from a single center were potential limitations of the findings.

DISCLOSURES:

The study received no outside funding. The researchers had no financial conflicts to disclose.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Eosinopenia and low ratio between eosinophil count (EC) and neutrophil count (NC) are potential indicators of infection for patients with inflammatory disease who are treated with tocilizumab.

METHODOLOGY:

• The researchers reviewed data from 163 patients treated for an inflammatory disease (mostly rheumatoid arthritis) with tocilizumab at a single center between 2009 and 2020.
• The study population included 41 patients with unscheduled hospitalizations for suspected infections. Patients’ median age was 59 years, and 83% were female.
• The researchers assessed the association in tocilizumab-treated patients between infections and eosinopenia (defined as EC < 0.05 g/L) and a low ratio between EC and NC, defined as EC/NC × 1000 < 11.8.

TAKEAWAY:

• Infectious diseases were diagnosed in 20 of the hospitalized patients (49%); the most common diseases were pneumonia (30%), joint or bone infections (25%), and gastrointestinal tract infections (15%).
• The median absolute EC at hospital admission was significantly lower for patients with infections than for those without infections (0.06 g/L vs 0.20 g/L).
• The median EC/NC × 1000 ratios were significantly lower in infected patients vs noninfected patients (6.54 vs 48.50).
• No differences appeared between patients with and without infections in age, sex, type of inflammatory disease, and steroid treatment.

IN PRACTICE:

“This original study suggests that all those easily available parameters should be used to maximize [sensitivity] in the screening of infection in patients undergoing treatment with IL-6 pathway antagonists,” the researchers wrote.

SOURCE:

The lead author on the study was Audrey Glatre, MD, of University Hospital Centre Reims, France. The study was published online in RMD Open on February 9.

LIMITATIONS:

The retrospective, observational design; relatively small study population; and use of data from a single center were potential limitations of the findings.

DISCLOSURES:

The study received no outside funding. The researchers had no financial conflicts to disclose.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Eosinopenia and low ratio between eosinophil count (EC) and neutrophil count (NC) are potential indicators of infection for patients with inflammatory disease who are treated with tocilizumab.

METHODOLOGY:

• The researchers reviewed data from 163 patients treated for an inflammatory disease (mostly rheumatoid arthritis) with tocilizumab at a single center between 2009 and 2020.
• The study population included 41 patients with unscheduled hospitalizations for suspected infections. Patients’ median age was 59 years, and 83% were female.
• The researchers assessed the association in tocilizumab-treated patients between infections and eosinopenia (defined as EC < 0.05 g/L) and a low ratio between EC and NC, defined as EC/NC × 1000 < 11.8.

TAKEAWAY:

• Infectious diseases were diagnosed in 20 of the hospitalized patients (49%); the most common diseases were pneumonia (30%), joint or bone infections (25%), and gastrointestinal tract infections (15%).
• The median absolute EC at hospital admission was significantly lower for patients with infections than for those without infections (0.06 g/L vs 0.20 g/L).
• The median EC/NC × 1000 ratios were significantly lower in infected patients vs noninfected patients (6.54 vs 48.50).
• No differences appeared between patients with and without infections in age, sex, type of inflammatory disease, and steroid treatment.

IN PRACTICE:

“This original study suggests that all those easily available parameters should be used to maximize [sensitivity] in the screening of infection in patients undergoing treatment with IL-6 pathway antagonists,” the researchers wrote.

SOURCE:

The lead author on the study was Audrey Glatre, MD, of University Hospital Centre Reims, France. The study was published online in RMD Open on February 9.

LIMITATIONS:

The retrospective, observational design; relatively small study population; and use of data from a single center were potential limitations of the findings.

DISCLOSURES:

The study received no outside funding. The researchers had no financial conflicts to disclose.
 

A version of this article appeared on Medscape.com.

Communicating bad news to patients is one of the most stressful and challenging clinical tasks for any physician, regardless of his or her specialty. Delivering bad news to a patient or their close relative is demanding because the information provided during the dialogue can substantially alter the person’s perspective on life. This task is more frequent for physicians caring for oncology patients and can also affect the physician’s emotional state.

The manner in which bad news is communicated plays a significant role in the psychological burden on the patient, and various communication techniques and guidelines have been developed to enable physicians to perform this difficult task effectively.

Revealing bad news in person whenever possible, to address the emotional responses of patients or relatives, is part of the prevailing expert recommendations. However, it has been acknowledged that in certain situations, communicating bad news over the phone is more feasible.

Since the beginning of the COVID-19 pandemic, the disclosure of bad news over the phone has become a necessary substitute for in-person visits and an integral part of clinical practice worldwide. It remains to be clarified what the real psychological impact on patients and their closest relatives is when delivering bad news over the phone compared with delivering it in person.

Right and Wrong Ways

The most popular guideline for communicating bad news is SPIKES, a six-phase protocol with a special application for cancer patients. It is used in various countries (eg, the United States, France, and Germany) as a guide for this sensitive practice and for training in communication skills in this context. The SPIKES acronym refers to the following six recommended steps for delivering bad news:

• Setting: Set up the conversation.
• Perception: Assess the patient’s perception.
• Invitation: Ask the patient what he or she would like to know.
• Knowledge: Provide the patient with knowledge and information, breaking it down into small parts.
• Emotions: Acknowledge and empathetically address the patient’s emotions.
• Strategy and Summary: Summarize and define a medical action plan.

The lesson from SPIKES is that when a person experiences strong emotions, it is difficult to continue discussing anything, and they will struggle to hear anything. Allowing for silence is fundamental. In addition, empathy allows the patient to express his or her feelings and concerns, as well as provide support. The aim is not to argue but to allow the expression of emotions without criticism. However, these recommendations are primarily based on expert opinion and less on empirical evidence, due to the difficulty of studies in assessing patient outcomes in various phases of these protocols.

A recent study analyzed the differences in psychological distress between patients who received bad news over the phone vs those who received it in person. The study was a systematic review and meta-analysis.

The investigators examined 5944 studies, including 11 qualitative analysis studies, nine meta-analyses, and four randomized controlled trials.

In a set of studies ranging from moderate to good quality, no difference in psychological distress was found when bad news was disclosed over the phone compared with in person, regarding anxiety, depression, and posttraumatic stress disorder.

There was no average difference in patient satisfaction levels when bad news was delivered over the phone compared with in person. The risk for dissatisfaction was similar between groups.

Clinical Practice Guidelines

The demand for telemedicine, including the disclosure of bad news, is growing despite the limited knowledge of potential adverse effects. The results of existing studies suggest that the mode of disclosure may play a secondary role, and the manner in which bad news is communicated may be more important.

Therefore, it is paramount to prepare patients or their families for the possibility of receiving bad news well in advance and, during the conversation, to ensure first and foremost that they are in an appropriate environment. The structure and content of the conversation may be relevant, and adhering to dedicated communication strategies can be a wise choice for the physician and the interlocutor.

This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Communicating bad news to patients is one of the most stressful and challenging clinical tasks for any physician, regardless of his or her specialty. Delivering bad news to a patient or their close relative is demanding because the information provided during the dialogue can substantially alter the person’s perspective on life. This task is more frequent for physicians caring for oncology patients and can also affect the physician’s emotional state.

The manner in which bad news is communicated plays a significant role in the psychological burden on the patient, and various communication techniques and guidelines have been developed to enable physicians to perform this difficult task effectively.

Revealing bad news in person whenever possible, to address the emotional responses of patients or relatives, is part of the prevailing expert recommendations. However, it has been acknowledged that in certain situations, communicating bad news over the phone is more feasible.

Since the beginning of the COVID-19 pandemic, the disclosure of bad news over the phone has become a necessary substitute for in-person visits and an integral part of clinical practice worldwide. It remains to be clarified what the real psychological impact on patients and their closest relatives is when delivering bad news over the phone compared with delivering it in person.

Right and Wrong Ways

The most popular guideline for communicating bad news is SPIKES, a six-phase protocol with a special application for cancer patients. It is used in various countries (eg, the United States, France, and Germany) as a guide for this sensitive practice and for training in communication skills in this context. The SPIKES acronym refers to the following six recommended steps for delivering bad news:

• Setting: Set up the conversation.
• Perception: Assess the patient’s perception.
• Invitation: Ask the patient what he or she would like to know.
• Knowledge: Provide the patient with knowledge and information, breaking it down into small parts.
• Emotions: Acknowledge and empathetically address the patient’s emotions.
• Strategy and Summary: Summarize and define a medical action plan.

The lesson from SPIKES is that when a person experiences strong emotions, it is difficult to continue discussing anything, and they will struggle to hear anything. Allowing for silence is fundamental. In addition, empathy allows the patient to express his or her feelings and concerns, as well as provide support. The aim is not to argue but to allow the expression of emotions without criticism. However, these recommendations are primarily based on expert opinion and less on empirical evidence, due to the difficulty of studies in assessing patient outcomes in various phases of these protocols.

A recent study analyzed the differences in psychological distress between patients who received bad news over the phone vs those who received it in person. The study was a systematic review and meta-analysis.

The investigators examined 5944 studies, including 11 qualitative analysis studies, nine meta-analyses, and four randomized controlled trials.

In a set of studies ranging from moderate to good quality, no difference in psychological distress was found when bad news was disclosed over the phone compared with in person, regarding anxiety, depression, and posttraumatic stress disorder.

There was no average difference in patient satisfaction levels when bad news was delivered over the phone compared with in person. The risk for dissatisfaction was similar between groups.

Clinical Practice Guidelines

The demand for telemedicine, including the disclosure of bad news, is growing despite the limited knowledge of potential adverse effects. The results of existing studies suggest that the mode of disclosure may play a secondary role, and the manner in which bad news is communicated may be more important.

Therefore, it is paramount to prepare patients or their families for the possibility of receiving bad news well in advance and, during the conversation, to ensure first and foremost that they are in an appropriate environment. The structure and content of the conversation may be relevant, and adhering to dedicated communication strategies can be a wise choice for the physician and the interlocutor.

This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Communicating bad news to patients is one of the most stressful and challenging clinical tasks for any physician, regardless of his or her specialty. Delivering bad news to a patient or their close relative is demanding because the information provided during the dialogue can substantially alter the person’s perspective on life. This task is more frequent for physicians caring for oncology patients and can also affect the physician’s emotional state.

The manner in which bad news is communicated plays a significant role in the psychological burden on the patient, and various communication techniques and guidelines have been developed to enable physicians to perform this difficult task effectively.

Revealing bad news in person whenever possible, to address the emotional responses of patients or relatives, is part of the prevailing expert recommendations. However, it has been acknowledged that in certain situations, communicating bad news over the phone is more feasible.

Since the beginning of the COVID-19 pandemic, the disclosure of bad news over the phone has become a necessary substitute for in-person visits and an integral part of clinical practice worldwide. It remains to be clarified what the real psychological impact on patients and their closest relatives is when delivering bad news over the phone compared with delivering it in person.

Right and Wrong Ways

The most popular guideline for communicating bad news is SPIKES, a six-phase protocol with a special application for cancer patients. It is used in various countries (eg, the United States, France, and Germany) as a guide for this sensitive practice and for training in communication skills in this context. The SPIKES acronym refers to the following six recommended steps for delivering bad news:

• Setting: Set up the conversation.
• Perception: Assess the patient’s perception.
• Invitation: Ask the patient what he or she would like to know.
• Knowledge: Provide the patient with knowledge and information, breaking it down into small parts.
• Emotions: Acknowledge and empathetically address the patient’s emotions.
• Strategy and Summary: Summarize and define a medical action plan.

The lesson from SPIKES is that when a person experiences strong emotions, it is difficult to continue discussing anything, and they will struggle to hear anything. Allowing for silence is fundamental. In addition, empathy allows the patient to express his or her feelings and concerns, as well as provide support. The aim is not to argue but to allow the expression of emotions without criticism. However, these recommendations are primarily based on expert opinion and less on empirical evidence, due to the difficulty of studies in assessing patient outcomes in various phases of these protocols.

A recent study analyzed the differences in psychological distress between patients who received bad news over the phone vs those who received it in person. The study was a systematic review and meta-analysis.

The investigators examined 5944 studies, including 11 qualitative analysis studies, nine meta-analyses, and four randomized controlled trials.

In a set of studies ranging from moderate to good quality, no difference in psychological distress was found when bad news was disclosed over the phone compared with in person, regarding anxiety, depression, and posttraumatic stress disorder.

There was no average difference in patient satisfaction levels when bad news was delivered over the phone compared with in person. The risk for dissatisfaction was similar between groups.

Clinical Practice Guidelines

The demand for telemedicine, including the disclosure of bad news, is growing despite the limited knowledge of potential adverse effects. The results of existing studies suggest that the mode of disclosure may play a secondary role, and the manner in which bad news is communicated may be more important.

Therefore, it is paramount to prepare patients or their families for the possibility of receiving bad news well in advance and, during the conversation, to ensure first and foremost that they are in an appropriate environment. The structure and content of the conversation may be relevant, and adhering to dedicated communication strategies can be a wise choice for the physician and the interlocutor.

This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Campaigners for greater transparency in medical science have reiterated calls for more to be done to avoid “medical research waste” after an investigation found that results from more than a fifth of clinical trials across five Nordic countries have never been made public.

A study found that results from 475 clinical trials in Denmark, Iceland, Finland, Norway, and Sweden — involving almost 84,000 participants — were never made public in any form.

Nonpublication of clinical trial results wastes public money, harms patients, and undermines public health, the researchers said. 

There is already a well-defined ethical responsibility to publish trial results. Article 36 of the Declaration of Helsinki on Ethical Principles for Medical Research Involving Human Subjects states that “researchers have a duty to make publicly available the results of their research on human subjects,” and World Health Organization best practice protocols call for results to be uploaded onto trial registries within 12 months of trial completion.
 

Research Waste Is a ‘Pervasive Problem’

So, how and why do so many trials end up gathering dust in a drawer? The latest study, published February 5 as a preprint, evaluated the reporting outcomes of 2113 clinical trials at medical universities and university hospitals in Nordic countries between 2016 and 2019. It found that across the five countries, 22% of all clinical trial results had not been shared. Furthermore, only 27% of all trial results were made public, either on registries or in journals, within 12 months. Even 2 years after trials ended, only around half of results (51.7%) had been put into the public domain.

The authors concluded that missing and delayed results from academically-led clinical trials was a “pervasive problem” in Nordic countries and that institutions, funding bodies, and policymakers needed to ensure that regulations around reporting results were adhered to so that important findings are not lost.

Study first author, Gustav Nilsonne, MD, PHD, from the Department of Clinical Neuroscience at the Karolinska Institutet, Sweden, told this news organization: “Most people I talk to — most colleagues who are clinical scientists — tend to think that the main reason is that negative results are not as interesting to publish and therefore they get lower priority, and they get published later and sometimes not at all.”

Experts stressed that the problem is not confined to Nordic countries and that wasted medical research persists elsewhere in Europe and remains a global problem. For instance, a report published in the Journal of Clinical Epidemiology found that 30% of German trials completed between 2014 and 2017 remained unpublished 5 years after completion.
 

The Case for Laws, Monitoring, and Fines

Till Bruckner, PHD, from TranspariMED, which campaigns to end evidence distortion in medicine, told this news organization: “What is needed to comprehensively fix the problem is a national legal requirement to make all trial results public, coupled with effective monitoring, and followed by sanctions in the rare cases where institutions refuse to comply.” 

Dr. Nilsonne added: “We have argued that the sponsors need to take greater responsibility, but also that there needs to be somebody whose job it is to monitor clinical trials reporting. It shouldn’t have to be that we do this as researchers on a shoestring with no dedicated resources. It should be somebody’s job.”

Since January 31, 2023, all initial clinical trial applications in the European Union must be submitted through the EU Clinical Trials Information System. Dr. Bruckner said that “the picture is not yet clear” in Europe, as the first trial results under the system are not expected until later this year. Even then, enforcement lies with regulators in individual countries. And while Denmark has already indicated it will enforce the regulations, he warned that other countries “might turn a blind eye.”

He pointed out that existing laws don’t apply to all types of trials. “That means that for many trials, nobody is legally responsible for ensuring that results are made public, and no government agency has any oversight or mandate,” he said.

Outside the EU, the United Kingdom has helped lead the way through the NHS Health Research Authority (HRA), which registers trials run in the country. One year after a trial has been completed, the HRA checks to see if the results have been uploaded to the registry and issues reminders if they haven’t.

In an update of its work in January, the authority said that compliance had hovered at just below 90% between 2018 and 2021 but that it was working to increase this to 100% by working with stakeholders across the research sector.

Dr. Nilsonne considers the UK system of central registration and follow-up an attractive option. “I would love to see something along those lines in other countries too,” he said.
 

‘Rampant Noncompliance’ in the United States

In the United States, a requirement to make trial results public is backed by law. Despite this, there’s evidence of “rampant noncompliance” and minimal government action, according to Megan Curtin from Universities Allied for Essential Medicines (UAEM), which has been tracking the issue in the United States and working to push universities and others to make their findings available.

The US Food and Drug Administration (FDA) shares responsibility with the National Institutes of Health for enforcement of clinical trial results reporting, but the UAEM says nearly 4000 trials are currently out of compliance with reporting requirements. In January last year, the UAEM copublished a report with the National Center for Health Research and TranspariMED, which found that 3627 American children participated in clinical trials whose results remain unreported.

The FDA can levy a fine of up to $10,000 USD for a violation of the law, but UAEM said that, as of January 2023, the FDA had sent only 92 preliminary notices of noncompliance and four notices of noncompliance. “A clear difference between the EU field of clinical trial operation and US clinical trials is that there are clear laws for reporting within 12 months, which can be enforced, but they’re not being enforced by the FDA,” Ms. Curtin told this news organization.

The UAEM is pushing the FDA to issue a minimum of 250 preliminary notices of noncompliance each year to noncompliant trial sponsors.

Dr. Nilsonne said: “I do believe we have a great responsibility to the patients that do contribute. We need to make sure that the harms and risks that a clinical trial entails are really balanced by knowledge gain, and if the results are never reported, then we can’t have a knowledge gain.”
 

A version of this article appeared on Medscape.com.

Campaigners for greater transparency in medical science have reiterated calls for more to be done to avoid “medical research waste” after an investigation found that results from more than a fifth of clinical trials across five Nordic countries have never been made public.

A study found that results from 475 clinical trials in Denmark, Iceland, Finland, Norway, and Sweden — involving almost 84,000 participants — were never made public in any form.

Nonpublication of clinical trial results wastes public money, harms patients, and undermines public health, the researchers said. 

There is already a well-defined ethical responsibility to publish trial results. Article 36 of the Declaration of Helsinki on Ethical Principles for Medical Research Involving Human Subjects states that “researchers have a duty to make publicly available the results of their research on human subjects,” and World Health Organization best practice protocols call for results to be uploaded onto trial registries within 12 months of trial completion.
 

Research Waste Is a ‘Pervasive Problem’

So, how and why do so many trials end up gathering dust in a drawer? The latest study, published February 5 as a preprint, evaluated the reporting outcomes of 2113 clinical trials at medical universities and university hospitals in Nordic countries between 2016 and 2019. It found that across the five countries, 22% of all clinical trial results had not been shared. Furthermore, only 27% of all trial results were made public, either on registries or in journals, within 12 months. Even 2 years after trials ended, only around half of results (51.7%) had been put into the public domain.

The authors concluded that missing and delayed results from academically-led clinical trials was a “pervasive problem” in Nordic countries and that institutions, funding bodies, and policymakers needed to ensure that regulations around reporting results were adhered to so that important findings are not lost.

Study first author, Gustav Nilsonne, MD, PHD, from the Department of Clinical Neuroscience at the Karolinska Institutet, Sweden, told this news organization: “Most people I talk to — most colleagues who are clinical scientists — tend to think that the main reason is that negative results are not as interesting to publish and therefore they get lower priority, and they get published later and sometimes not at all.”

Experts stressed that the problem is not confined to Nordic countries and that wasted medical research persists elsewhere in Europe and remains a global problem. For instance, a report published in the Journal of Clinical Epidemiology found that 30% of German trials completed between 2014 and 2017 remained unpublished 5 years after completion.
 

The Case for Laws, Monitoring, and Fines

Till Bruckner, PHD, from TranspariMED, which campaigns to end evidence distortion in medicine, told this news organization: “What is needed to comprehensively fix the problem is a national legal requirement to make all trial results public, coupled with effective monitoring, and followed by sanctions in the rare cases where institutions refuse to comply.” 

Dr. Nilsonne added: “We have argued that the sponsors need to take greater responsibility, but also that there needs to be somebody whose job it is to monitor clinical trials reporting. It shouldn’t have to be that we do this as researchers on a shoestring with no dedicated resources. It should be somebody’s job.”

Since January 31, 2023, all initial clinical trial applications in the European Union must be submitted through the EU Clinical Trials Information System. Dr. Bruckner said that “the picture is not yet clear” in Europe, as the first trial results under the system are not expected until later this year. Even then, enforcement lies with regulators in individual countries. And while Denmark has already indicated it will enforce the regulations, he warned that other countries “might turn a blind eye.”

He pointed out that existing laws don’t apply to all types of trials. “That means that for many trials, nobody is legally responsible for ensuring that results are made public, and no government agency has any oversight or mandate,” he said.

Outside the EU, the United Kingdom has helped lead the way through the NHS Health Research Authority (HRA), which registers trials run in the country. One year after a trial has been completed, the HRA checks to see if the results have been uploaded to the registry and issues reminders if they haven’t.

In an update of its work in January, the authority said that compliance had hovered at just below 90% between 2018 and 2021 but that it was working to increase this to 100% by working with stakeholders across the research sector.

Dr. Nilsonne considers the UK system of central registration and follow-up an attractive option. “I would love to see something along those lines in other countries too,” he said.
 

‘Rampant Noncompliance’ in the United States

In the United States, a requirement to make trial results public is backed by law. Despite this, there’s evidence of “rampant noncompliance” and minimal government action, according to Megan Curtin from Universities Allied for Essential Medicines (UAEM), which has been tracking the issue in the United States and working to push universities and others to make their findings available.

The US Food and Drug Administration (FDA) shares responsibility with the National Institutes of Health for enforcement of clinical trial results reporting, but the UAEM says nearly 4000 trials are currently out of compliance with reporting requirements. In January last year, the UAEM copublished a report with the National Center for Health Research and TranspariMED, which found that 3627 American children participated in clinical trials whose results remain unreported.

The FDA can levy a fine of up to $10,000 USD for a violation of the law, but UAEM said that, as of January 2023, the FDA had sent only 92 preliminary notices of noncompliance and four notices of noncompliance. “A clear difference between the EU field of clinical trial operation and US clinical trials is that there are clear laws for reporting within 12 months, which can be enforced, but they’re not being enforced by the FDA,” Ms. Curtin told this news organization.

The UAEM is pushing the FDA to issue a minimum of 250 preliminary notices of noncompliance each year to noncompliant trial sponsors.

Dr. Nilsonne said: “I do believe we have a great responsibility to the patients that do contribute. We need to make sure that the harms and risks that a clinical trial entails are really balanced by knowledge gain, and if the results are never reported, then we can’t have a knowledge gain.”
 

A version of this article appeared on Medscape.com.

Campaigners for greater transparency in medical science have reiterated calls for more to be done to avoid “medical research waste” after an investigation found that results from more than a fifth of clinical trials across five Nordic countries have never been made public.

A study found that results from 475 clinical trials in Denmark, Iceland, Finland, Norway, and Sweden — involving almost 84,000 participants — were never made public in any form.

Nonpublication of clinical trial results wastes public money, harms patients, and undermines public health, the researchers said. 

There is already a well-defined ethical responsibility to publish trial results. Article 36 of the Declaration of Helsinki on Ethical Principles for Medical Research Involving Human Subjects states that “researchers have a duty to make publicly available the results of their research on human subjects,” and World Health Organization best practice protocols call for results to be uploaded onto trial registries within 12 months of trial completion.
 

Research Waste Is a ‘Pervasive Problem’

So, how and why do so many trials end up gathering dust in a drawer? The latest study, published February 5 as a preprint, evaluated the reporting outcomes of 2113 clinical trials at medical universities and university hospitals in Nordic countries between 2016 and 2019. It found that across the five countries, 22% of all clinical trial results had not been shared. Furthermore, only 27% of all trial results were made public, either on registries or in journals, within 12 months. Even 2 years after trials ended, only around half of results (51.7%) had been put into the public domain.

The authors concluded that missing and delayed results from academically-led clinical trials was a “pervasive problem” in Nordic countries and that institutions, funding bodies, and policymakers needed to ensure that regulations around reporting results were adhered to so that important findings are not lost.

Study first author, Gustav Nilsonne, MD, PHD, from the Department of Clinical Neuroscience at the Karolinska Institutet, Sweden, told this news organization: “Most people I talk to — most colleagues who are clinical scientists — tend to think that the main reason is that negative results are not as interesting to publish and therefore they get lower priority, and they get published later and sometimes not at all.”

Experts stressed that the problem is not confined to Nordic countries and that wasted medical research persists elsewhere in Europe and remains a global problem. For instance, a report published in the Journal of Clinical Epidemiology found that 30% of German trials completed between 2014 and 2017 remained unpublished 5 years after completion.
 

The Case for Laws, Monitoring, and Fines

Till Bruckner, PHD, from TranspariMED, which campaigns to end evidence distortion in medicine, told this news organization: “What is needed to comprehensively fix the problem is a national legal requirement to make all trial results public, coupled with effective monitoring, and followed by sanctions in the rare cases where institutions refuse to comply.” 

Dr. Nilsonne added: “We have argued that the sponsors need to take greater responsibility, but also that there needs to be somebody whose job it is to monitor clinical trials reporting. It shouldn’t have to be that we do this as researchers on a shoestring with no dedicated resources. It should be somebody’s job.”

Since January 31, 2023, all initial clinical trial applications in the European Union must be submitted through the EU Clinical Trials Information System. Dr. Bruckner said that “the picture is not yet clear” in Europe, as the first trial results under the system are not expected until later this year. Even then, enforcement lies with regulators in individual countries. And while Denmark has already indicated it will enforce the regulations, he warned that other countries “might turn a blind eye.”

He pointed out that existing laws don’t apply to all types of trials. “That means that for many trials, nobody is legally responsible for ensuring that results are made public, and no government agency has any oversight or mandate,” he said.

Outside the EU, the United Kingdom has helped lead the way through the NHS Health Research Authority (HRA), which registers trials run in the country. One year after a trial has been completed, the HRA checks to see if the results have been uploaded to the registry and issues reminders if they haven’t.

In an update of its work in January, the authority said that compliance had hovered at just below 90% between 2018 and 2021 but that it was working to increase this to 100% by working with stakeholders across the research sector.

Dr. Nilsonne considers the UK system of central registration and follow-up an attractive option. “I would love to see something along those lines in other countries too,” he said.
 

‘Rampant Noncompliance’ in the United States

In the United States, a requirement to make trial results public is backed by law. Despite this, there’s evidence of “rampant noncompliance” and minimal government action, according to Megan Curtin from Universities Allied for Essential Medicines (UAEM), which has been tracking the issue in the United States and working to push universities and others to make their findings available.

The US Food and Drug Administration (FDA) shares responsibility with the National Institutes of Health for enforcement of clinical trial results reporting, but the UAEM says nearly 4000 trials are currently out of compliance with reporting requirements. In January last year, the UAEM copublished a report with the National Center for Health Research and TranspariMED, which found that 3627 American children participated in clinical trials whose results remain unreported.

The FDA can levy a fine of up to $10,000 USD for a violation of the law, but UAEM said that, as of January 2023, the FDA had sent only 92 preliminary notices of noncompliance and four notices of noncompliance. “A clear difference between the EU field of clinical trial operation and US clinical trials is that there are clear laws for reporting within 12 months, which can be enforced, but they’re not being enforced by the FDA,” Ms. Curtin told this news organization.

The UAEM is pushing the FDA to issue a minimum of 250 preliminary notices of noncompliance each year to noncompliant trial sponsors.

Dr. Nilsonne said: “I do believe we have a great responsibility to the patients that do contribute. We need to make sure that the harms and risks that a clinical trial entails are really balanced by knowledge gain, and if the results are never reported, then we can’t have a knowledge gain.”
 

A version of this article appeared on Medscape.com.

Among patients with psoriasis, the risk of mortality was strongly associated with hepatic injury, cardiovascular disease, and psychiatric affective disorders, but was reduced among those who received systemic therapy with biologics, researchers from Canada report.

Those are key findings from a large retrospective registry study of patients with psoriasis, published in The Journal of the American Academy of Dermatology.

“Psoriasis, a chronic inflammatory condition affecting approximately 3% of the western populations, bears a higher risk of mortality compared to healthy individuals, possibly by inducing systemic inflammation associated with numerous comorbidities, especially cardiovascular diseases, metabolic syndrome, and others,” wrote corresponding author Robert Gniadecki, MD, PhD, of the division of dermatology at the University of Alberta, Canada, and colleagues. “It has been argued that the use of systemic immunomodulatory agents quenches systemic inflammation and potentially improves patient survival. However, the evidence to support this hypothesis is limited.”

To investigate the impact of comorbidities and systemic therapies on all-cause mortality in psoriasis, the researchers used the Alberta Health Services Data Repository of Reporting database from January 1, 2012, to June 1, 2019, which represents a population base of 4.47 million individuals. They extracted data on 18,618 psoriasis cases and 55,854 controls, stratified cases according to the Charlson Comorbidity Index (CCI), a surrogate measure for comorbidity burden, and by the type of therapy received, and conducted statistical analyses including Cox proportional hazards regression to determine absolute hazard ratios representing relative effects of specific demographic and comorbidity factors on mortality within groups.

The median age in both cohorts was 48 years, and 51% were male. The researchers observed that mortality in the psoriasis cohort was significantly higher than in the controls (5.7% vs. 3.8%, respectively; P < .05), with a median age at the time of death of 72 vs. 74.4 years.

The CCI and comorbidities strongly predicted mortality, especially drug-induced liver injury (hazard ratio [HR], 1.78), bipolar disorder and suicidal ideation (HR, 1.24-1.58), and major cardiovascular diseases, which included myocardial infarction (MI), congestive heart failure (CHF), and cerebrovascular disease (CVA) (HR, 1.2-1.4).

Among patients in the psoriasis cohort, survival of those treated with biologic agents was higher than in controls, even after matching for CCI (3.2% vs. 4.4%, respectively, P < .05). “These patients also exhibit reduced overall mortality compared to those treated with methotrexate or topical agents,” Dr. Gniadecki and colleagues wrote. “There was no difference in mortality between methotrexate patients and the topical therapy patients, but any of those treatment groups had superior survival compared to the no-treatment cohort.”

They added that despite better survival among patients treated with biologic agents, no significant improvements were detected in their comorbidity profiles. “Notably, the frequency of major cardiovascular disease (MI, CHF, CVA) was the same as in the controls, and overall, the frequency of diseases coded as cardiovascular was slightly increased,” they wrote.

The fact that some factors could not be measured, including the type and severity of psoriasis, response to treatment, smoking history, and alcohol intake, was a study limitation, they noted.

Joel M. Gelfand, MD, director of the psoriasis and phototherapy treatment center at the University of Pennsylvania, Philadelphia, who was asked to comment on the analysis, said the study confirms prior work indicating that having psoriasis is a predictor of mortality. In addition, “there is a strong healthy user affect among patients who take and stay on biologics for psoriasis,” he told this news organization.

Courtesy Dr. Gelfand

Among patients with psoriasis, the risk of mortality was strongly associated with hepatic injury, cardiovascular disease, and psychiatric affective disorders, but was reduced among those who received systemic therapy with biologics, researchers from Canada report.

Those are key findings from a large retrospective registry study of patients with psoriasis, published in The Journal of the American Academy of Dermatology.

“Psoriasis, a chronic inflammatory condition affecting approximately 3% of the western populations, bears a higher risk of mortality compared to healthy individuals, possibly by inducing systemic inflammation associated with numerous comorbidities, especially cardiovascular diseases, metabolic syndrome, and others,” wrote corresponding author Robert Gniadecki, MD, PhD, of the division of dermatology at the University of Alberta, Canada, and colleagues. “It has been argued that the use of systemic immunomodulatory agents quenches systemic inflammation and potentially improves patient survival. However, the evidence to support this hypothesis is limited.”

To investigate the impact of comorbidities and systemic therapies on all-cause mortality in psoriasis, the researchers used the Alberta Health Services Data Repository of Reporting database from January 1, 2012, to June 1, 2019, which represents a population base of 4.47 million individuals. They extracted data on 18,618 psoriasis cases and 55,854 controls, stratified cases according to the Charlson Comorbidity Index (CCI), a surrogate measure for comorbidity burden, and by the type of therapy received, and conducted statistical analyses including Cox proportional hazards regression to determine absolute hazard ratios representing relative effects of specific demographic and comorbidity factors on mortality within groups.

The median age in both cohorts was 48 years, and 51% were male. The researchers observed that mortality in the psoriasis cohort was significantly higher than in the controls (5.7% vs. 3.8%, respectively; P < .05), with a median age at the time of death of 72 vs. 74.4 years.

The CCI and comorbidities strongly predicted mortality, especially drug-induced liver injury (hazard ratio [HR], 1.78), bipolar disorder and suicidal ideation (HR, 1.24-1.58), and major cardiovascular diseases, which included myocardial infarction (MI), congestive heart failure (CHF), and cerebrovascular disease (CVA) (HR, 1.2-1.4).

Among patients in the psoriasis cohort, survival of those treated with biologic agents was higher than in controls, even after matching for CCI (3.2% vs. 4.4%, respectively, P < .05). “These patients also exhibit reduced overall mortality compared to those treated with methotrexate or topical agents,” Dr. Gniadecki and colleagues wrote. “There was no difference in mortality between methotrexate patients and the topical therapy patients, but any of those treatment groups had superior survival compared to the no-treatment cohort.”

They added that despite better survival among patients treated with biologic agents, no significant improvements were detected in their comorbidity profiles. “Notably, the frequency of major cardiovascular disease (MI, CHF, CVA) was the same as in the controls, and overall, the frequency of diseases coded as cardiovascular was slightly increased,” they wrote.

The fact that some factors could not be measured, including the type and severity of psoriasis, response to treatment, smoking history, and alcohol intake, was a study limitation, they noted.

Joel M. Gelfand, MD, director of the psoriasis and phototherapy treatment center at the University of Pennsylvania, Philadelphia, who was asked to comment on the analysis, said the study confirms prior work indicating that having psoriasis is a predictor of mortality. In addition, “there is a strong healthy user affect among patients who take and stay on biologics for psoriasis,” he told this news organization.

Courtesy Dr. Gelfand

Among patients with psoriasis, the risk of mortality was strongly associated with hepatic injury, cardiovascular disease, and psychiatric affective disorders, but was reduced among those who received systemic therapy with biologics, researchers from Canada report.

Those are key findings from a large retrospective registry study of patients with psoriasis, published in The Journal of the American Academy of Dermatology.

“Psoriasis, a chronic inflammatory condition affecting approximately 3% of the western populations, bears a higher risk of mortality compared to healthy individuals, possibly by inducing systemic inflammation associated with numerous comorbidities, especially cardiovascular diseases, metabolic syndrome, and others,” wrote corresponding author Robert Gniadecki, MD, PhD, of the division of dermatology at the University of Alberta, Canada, and colleagues. “It has been argued that the use of systemic immunomodulatory agents quenches systemic inflammation and potentially improves patient survival. However, the evidence to support this hypothesis is limited.”

To investigate the impact of comorbidities and systemic therapies on all-cause mortality in psoriasis, the researchers used the Alberta Health Services Data Repository of Reporting database from January 1, 2012, to June 1, 2019, which represents a population base of 4.47 million individuals. They extracted data on 18,618 psoriasis cases and 55,854 controls, stratified cases according to the Charlson Comorbidity Index (CCI), a surrogate measure for comorbidity burden, and by the type of therapy received, and conducted statistical analyses including Cox proportional hazards regression to determine absolute hazard ratios representing relative effects of specific demographic and comorbidity factors on mortality within groups.

The median age in both cohorts was 48 years, and 51% were male. The researchers observed that mortality in the psoriasis cohort was significantly higher than in the controls (5.7% vs. 3.8%, respectively; P < .05), with a median age at the time of death of 72 vs. 74.4 years.

The CCI and comorbidities strongly predicted mortality, especially drug-induced liver injury (hazard ratio [HR], 1.78), bipolar disorder and suicidal ideation (HR, 1.24-1.58), and major cardiovascular diseases, which included myocardial infarction (MI), congestive heart failure (CHF), and cerebrovascular disease (CVA) (HR, 1.2-1.4).

Among patients in the psoriasis cohort, survival of those treated with biologic agents was higher than in controls, even after matching for CCI (3.2% vs. 4.4%, respectively, P < .05). “These patients also exhibit reduced overall mortality compared to those treated with methotrexate or topical agents,” Dr. Gniadecki and colleagues wrote. “There was no difference in mortality between methotrexate patients and the topical therapy patients, but any of those treatment groups had superior survival compared to the no-treatment cohort.”

They added that despite better survival among patients treated with biologic agents, no significant improvements were detected in their comorbidity profiles. “Notably, the frequency of major cardiovascular disease (MI, CHF, CVA) was the same as in the controls, and overall, the frequency of diseases coded as cardiovascular was slightly increased,” they wrote.

The fact that some factors could not be measured, including the type and severity of psoriasis, response to treatment, smoking history, and alcohol intake, was a study limitation, they noted.

Joel M. Gelfand, MD, director of the psoriasis and phototherapy treatment center at the University of Pennsylvania, Philadelphia, who was asked to comment on the analysis, said the study confirms prior work indicating that having psoriasis is a predictor of mortality. In addition, “there is a strong healthy user affect among patients who take and stay on biologics for psoriasis,” he told this news organization.

Courtesy Dr. Gelfand

Patients with Cushing disease have an increased risk for new-onset autoimmune disease in the 3 years after surgical remission, according to a new retrospective study published on February 20 in Annals of Internal Medicine.

Outcomes for patients with Cushing disease were compared against those with nonfunctioning pituitary adenomas (NFPAs). New-onset autoimmune disease occurred in 10.4% with Cushing disease and 1.6% among patients with NFPA (hazard ratio, 7.80; 95% CI, 2.88-21.10).

“Understanding and recognizing new and recurrent autoimmune disease in this setting is important to avoid misclassifying such patients with glucocorticoid withdrawal syndrome, which could result in failure to treat underlying autoimmune disease, as well as erroneous diagnosis of steroid withdrawal cases,” wrote Dennis Delasi Nyanyo of Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues.

Given the general population’s annual incidence of major autoimmune diseases, estimated at about 100 cases per 100,000 people, and the 3-year incidence of 10.4% found in this study’s cohort, “our findings suggest that Cushing disease remission may trigger development of autoimmune disease,” the authors wrote.
 

Monitor Patients With Family History of Autoimmune Disease?

The study results were not necessarily surprising to Anthony P. Heaney, MD, PhD, an endocrinologist and professor of medicine at the University of California, Los Angeles, because past research has raised similar questions. The authors’ suggestion that the rapid postsurgical drop in cortisol that occurs as a result of treating Cushing disease becomes some sort of autoimmune trigger is interesting but remains speculative, Dr. Heaney pointed out.

If future evidence supports that possibility, “it would suggest, in terms of managing those patients in the postoperative setting, that there may be some merit to giving them higher concentrations of glucocorticoids for a short period of time,” Dr. Heaney said, thereby bringing their levels down more gradually rather than taking them off a cliff, in a sense. Or, if more evidence bears out the authors’ hypothesis, another approach might be treating patients with medicine to bring down the cortisol before surgery, though there are challenges to that approach, Dr. Heaney said.

At the same time, those who developed new autoimmune disease remain a small subset of patients with Cushing disease, so such approaches may become only potentially appropriate to consider in patients with risk factors, such as a family history of autoimmune disease.

The researchers conducted a retrospective chart review of adult patients who underwent transsphenoidal surgery for either Cushing disease or NFPA at Massachusetts General Hospital between 2005 and 2019.

The study involved 194 patients with Cushing disease who had postsurgical remission and at least one follow-up visit with a pituitary expert and 92 patients with NFPA who were matched to patients with Cushing disease based on age and sex. The authors regarded autoimmune disease diagnosed within 36 months of the surgery to be temporally associated with Cushing disease remission. Among the autoimmune diseases considered were “rheumatoid arthritis, Sjögren syndrome, systemic lupus erythematosus, autoimmune thyroiditis, celiac disease, psoriasis, vitiligo, autoimmune neuropathy, multiple sclerosis, myasthenia gravis, and ulcerative colitis.”

Patients differed in average body mass index and tumor size, but family history of autoimmune disease was similar in both groups. Average BMI was 34.5 in the Cushing group and 29.5 in the NFPA group. Average tumor size was 5.7 mm in the Cushing group and 21.3 mm in the NFPA group.

Before surgery, 2.9% of patients with Cushing disease and 15.4% of patients with NFPA had central hypothyroidism, and 8% in the Cushing group and 56.8% in the NFPA group had hyperprolactinemia. Central adrenal insufficiency occurred in 11% with NFPA and in all with Cushing disease, by definition.

After surgery, 93.8% in the Cushing group and 16.5% in the NFPA group had adrenal insufficiency. In addition, patients with Cushing disease had lower postsurgical nadir serum cortisol levels (63.8 nmol/L) than those with NFPA (282.3 nmol/L).

Of the 17 patients with Cushing disease — all women — who developed autoimmune disease within 3 years, 6 had a personal history of autoimmune disease and 7 had a family history of it. In addition, 41.2% of them had adrenal insufficiency when they developed the new autoimmune disease. Among the diseases were six autoimmune thyroiditis cases, three Sjögren syndrome cases, and two autoimmune seronegative spondyloarthropathy.

Dr. Heaney said he found it interesting that more than half of the new autoimmune diseases in patients with Cushing disease were related to the thyroid. “In this kind of setting, where you have a patient who has been producing too much steroid over a period of time and then you take that away, it’s almost like you release a brake on the TSH [thyroid-stimulating hormone],” Dr. Heaney said. “So, there’s probably some rebound in TSH that occurs, and that could be driving the thyroiditis, to some extent, that we see in these patients.”

Only one patient with NFPA developed new-onset autoimmune disease, a woman who developed Graves disease 22 months after surgery. When the researchers excluded patients in both groups with central hypothyroidism, new-onset autoimmune disease was still significantly higher (11.4%) in the Cushing group than in the NFPA group (1.9%; HR, 7.02; 95% CI, 2.54-19.39).
 

Could Postoperative Adrenal Insufficiency Contribute to Risk?

Within the Cushing cohort, those who developed autoimmune disease had a lower BMI (31.8 vs 34.8) and larger tumor size (7.2 vs 5.6 mm) than those who didn’t develop new autoimmune disease. Patients who developed autoimmune disease also had a lower baseline urine free cortisol ratio (2.7 vs 6.3) before surgery and more family history of autoimmune disease (41.2% vs 20.9%) than those who didn’t develop one.

“The higher prevalence of adrenal insufficiency and the lower nadir serum cortisol levels in the Cushing disease group suggest that the postoperative adrenal insufficiency in the Cushing disease group might have contributed to autoimmune disease pathogenesis,” the authors wrote. “This finding is clinically significant because cortisol plays a pivotal role in modulating the immune system.”

Most postoperative management among patients with Cushing disease was similar, with all but one patient receiving 0.5 or 1 mg daily dexamethasone within the first week after surgery. (The one outlier received 5 mg daily prednisone.) However, fewer patients who developed autoimmune disease (17.6%) received supraphysiologic doses of glucocorticoid — equivalent to at least 25 mg hydrocortisone — compared with patients who didn’t develop autoimmune disease (41.8%).

“Although the daily average hydrocortisone equivalent replacement doses within the first month and during long-term follow-up were within the physiologic range in both subgroups, patients with Cushing disease who had autoimmune disease received slightly lower doses of glucocorticoid replacement within the first month after surgery,” the authors reported. “The immediate postoperative period might be a critical window where supraphysiologic glucocorticoids seem to be protective with regard to development of autoimmune disease,” they wrote, though they acknowledged the study’s retrospective design as a limitation in drawing that conclusion.

At the least, they suggested that new symptoms in patients with Cushing disease, particularly those with a family history of autoimmune disease, should prompt investigation of potential autoimmune disease.

Recordati Rare Diseases funded the study. The research was also conducted with support from Harvard Catalyst (the Harvard Clinical and Translational Science Center) as well as financial contributions from Harvard University and its affiliated academic healthcare centers. One author reported holding stocks in Pfizer and Amgen, and another reported receiving consulting fees from Corcept. Dr. Heaney reported receiving institutional grants for trials from Corcept, Ascendis, Crinetics, and Sparrow Pharm; serving on the advisory board for Xeris, Recordati, Corcept, Novo Nordisk, Lundbeck, and Crinetics; and serving as a speaker for Chiesi, Novo Nordisk, and Corcept.
 

A version of this article appeared on Medscape.com.

Patients with Cushing disease have an increased risk for new-onset autoimmune disease in the 3 years after surgical remission, according to a new retrospective study published on February 20 in Annals of Internal Medicine.

Outcomes for patients with Cushing disease were compared against those with nonfunctioning pituitary adenomas (NFPAs). New-onset autoimmune disease occurred in 10.4% with Cushing disease and 1.6% among patients with NFPA (hazard ratio, 7.80; 95% CI, 2.88-21.10).

“Understanding and recognizing new and recurrent autoimmune disease in this setting is important to avoid misclassifying such patients with glucocorticoid withdrawal syndrome, which could result in failure to treat underlying autoimmune disease, as well as erroneous diagnosis of steroid withdrawal cases,” wrote Dennis Delasi Nyanyo of Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues.

Given the general population’s annual incidence of major autoimmune diseases, estimated at about 100 cases per 100,000 people, and the 3-year incidence of 10.4% found in this study’s cohort, “our findings suggest that Cushing disease remission may trigger development of autoimmune disease,” the authors wrote.
 

Monitor Patients With Family History of Autoimmune Disease?

The study results were not necessarily surprising to Anthony P. Heaney, MD, PhD, an endocrinologist and professor of medicine at the University of California, Los Angeles, because past research has raised similar questions. The authors’ suggestion that the rapid postsurgical drop in cortisol that occurs as a result of treating Cushing disease becomes some sort of autoimmune trigger is interesting but remains speculative, Dr. Heaney pointed out.

If future evidence supports that possibility, “it would suggest, in terms of managing those patients in the postoperative setting, that there may be some merit to giving them higher concentrations of glucocorticoids for a short period of time,” Dr. Heaney said, thereby bringing their levels down more gradually rather than taking them off a cliff, in a sense. Or, if more evidence bears out the authors’ hypothesis, another approach might be treating patients with medicine to bring down the cortisol before surgery, though there are challenges to that approach, Dr. Heaney said.

At the same time, those who developed new autoimmune disease remain a small subset of patients with Cushing disease, so such approaches may become only potentially appropriate to consider in patients with risk factors, such as a family history of autoimmune disease.

The researchers conducted a retrospective chart review of adult patients who underwent transsphenoidal surgery for either Cushing disease or NFPA at Massachusetts General Hospital between 2005 and 2019.

The study involved 194 patients with Cushing disease who had postsurgical remission and at least one follow-up visit with a pituitary expert and 92 patients with NFPA who were matched to patients with Cushing disease based on age and sex. The authors regarded autoimmune disease diagnosed within 36 months of the surgery to be temporally associated with Cushing disease remission. Among the autoimmune diseases considered were “rheumatoid arthritis, Sjögren syndrome, systemic lupus erythematosus, autoimmune thyroiditis, celiac disease, psoriasis, vitiligo, autoimmune neuropathy, multiple sclerosis, myasthenia gravis, and ulcerative colitis.”

Patients differed in average body mass index and tumor size, but family history of autoimmune disease was similar in both groups. Average BMI was 34.5 in the Cushing group and 29.5 in the NFPA group. Average tumor size was 5.7 mm in the Cushing group and 21.3 mm in the NFPA group.

Before surgery, 2.9% of patients with Cushing disease and 15.4% of patients with NFPA had central hypothyroidism, and 8% in the Cushing group and 56.8% in the NFPA group had hyperprolactinemia. Central adrenal insufficiency occurred in 11% with NFPA and in all with Cushing disease, by definition.

After surgery, 93.8% in the Cushing group and 16.5% in the NFPA group had adrenal insufficiency. In addition, patients with Cushing disease had lower postsurgical nadir serum cortisol levels (63.8 nmol/L) than those with NFPA (282.3 nmol/L).

Of the 17 patients with Cushing disease — all women — who developed autoimmune disease within 3 years, 6 had a personal history of autoimmune disease and 7 had a family history of it. In addition, 41.2% of them had adrenal insufficiency when they developed the new autoimmune disease. Among the diseases were six autoimmune thyroiditis cases, three Sjögren syndrome cases, and two autoimmune seronegative spondyloarthropathy.

Dr. Heaney said he found it interesting that more than half of the new autoimmune diseases in patients with Cushing disease were related to the thyroid. “In this kind of setting, where you have a patient who has been producing too much steroid over a period of time and then you take that away, it’s almost like you release a brake on the TSH [thyroid-stimulating hormone],” Dr. Heaney said. “So, there’s probably some rebound in TSH that occurs, and that could be driving the thyroiditis, to some extent, that we see in these patients.”

Only one patient with NFPA developed new-onset autoimmune disease, a woman who developed Graves disease 22 months after surgery. When the researchers excluded patients in both groups with central hypothyroidism, new-onset autoimmune disease was still significantly higher (11.4%) in the Cushing group than in the NFPA group (1.9%; HR, 7.02; 95% CI, 2.54-19.39).
 

Could Postoperative Adrenal Insufficiency Contribute to Risk?

Within the Cushing cohort, those who developed autoimmune disease had a lower BMI (31.8 vs 34.8) and larger tumor size (7.2 vs 5.6 mm) than those who didn’t develop new autoimmune disease. Patients who developed autoimmune disease also had a lower baseline urine free cortisol ratio (2.7 vs 6.3) before surgery and more family history of autoimmune disease (41.2% vs 20.9%) than those who didn’t develop one.

“The higher prevalence of adrenal insufficiency and the lower nadir serum cortisol levels in the Cushing disease group suggest that the postoperative adrenal insufficiency in the Cushing disease group might have contributed to autoimmune disease pathogenesis,” the authors wrote. “This finding is clinically significant because cortisol plays a pivotal role in modulating the immune system.”

Most postoperative management among patients with Cushing disease was similar, with all but one patient receiving 0.5 or 1 mg daily dexamethasone within the first week after surgery. (The one outlier received 5 mg daily prednisone.) However, fewer patients who developed autoimmune disease (17.6%) received supraphysiologic doses of glucocorticoid — equivalent to at least 25 mg hydrocortisone — compared with patients who didn’t develop autoimmune disease (41.8%).

“Although the daily average hydrocortisone equivalent replacement doses within the first month and during long-term follow-up were within the physiologic range in both subgroups, patients with Cushing disease who had autoimmune disease received slightly lower doses of glucocorticoid replacement within the first month after surgery,” the authors reported. “The immediate postoperative period might be a critical window where supraphysiologic glucocorticoids seem to be protective with regard to development of autoimmune disease,” they wrote, though they acknowledged the study’s retrospective design as a limitation in drawing that conclusion.

At the least, they suggested that new symptoms in patients with Cushing disease, particularly those with a family history of autoimmune disease, should prompt investigation of potential autoimmune disease.

Recordati Rare Diseases funded the study. The research was also conducted with support from Harvard Catalyst (the Harvard Clinical and Translational Science Center) as well as financial contributions from Harvard University and its affiliated academic healthcare centers. One author reported holding stocks in Pfizer and Amgen, and another reported receiving consulting fees from Corcept. Dr. Heaney reported receiving institutional grants for trials from Corcept, Ascendis, Crinetics, and Sparrow Pharm; serving on the advisory board for Xeris, Recordati, Corcept, Novo Nordisk, Lundbeck, and Crinetics; and serving as a speaker for Chiesi, Novo Nordisk, and Corcept.
 

A version of this article appeared on Medscape.com.

Patients with Cushing disease have an increased risk for new-onset autoimmune disease in the 3 years after surgical remission, according to a new retrospective study published on February 20 in Annals of Internal Medicine.

Outcomes for patients with Cushing disease were compared against those with nonfunctioning pituitary adenomas (NFPAs). New-onset autoimmune disease occurred in 10.4% with Cushing disease and 1.6% among patients with NFPA (hazard ratio, 7.80; 95% CI, 2.88-21.10).

“Understanding and recognizing new and recurrent autoimmune disease in this setting is important to avoid misclassifying such patients with glucocorticoid withdrawal syndrome, which could result in failure to treat underlying autoimmune disease, as well as erroneous diagnosis of steroid withdrawal cases,” wrote Dennis Delasi Nyanyo of Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues.

Given the general population’s annual incidence of major autoimmune diseases, estimated at about 100 cases per 100,000 people, and the 3-year incidence of 10.4% found in this study’s cohort, “our findings suggest that Cushing disease remission may trigger development of autoimmune disease,” the authors wrote.
 

Monitor Patients With Family History of Autoimmune Disease?

The study results were not necessarily surprising to Anthony P. Heaney, MD, PhD, an endocrinologist and professor of medicine at the University of California, Los Angeles, because past research has raised similar questions. The authors’ suggestion that the rapid postsurgical drop in cortisol that occurs as a result of treating Cushing disease becomes some sort of autoimmune trigger is interesting but remains speculative, Dr. Heaney pointed out.

If future evidence supports that possibility, “it would suggest, in terms of managing those patients in the postoperative setting, that there may be some merit to giving them higher concentrations of glucocorticoids for a short period of time,” Dr. Heaney said, thereby bringing their levels down more gradually rather than taking them off a cliff, in a sense. Or, if more evidence bears out the authors’ hypothesis, another approach might be treating patients with medicine to bring down the cortisol before surgery, though there are challenges to that approach, Dr. Heaney said.

At the same time, those who developed new autoimmune disease remain a small subset of patients with Cushing disease, so such approaches may become only potentially appropriate to consider in patients with risk factors, such as a family history of autoimmune disease.

The researchers conducted a retrospective chart review of adult patients who underwent transsphenoidal surgery for either Cushing disease or NFPA at Massachusetts General Hospital between 2005 and 2019.

The study involved 194 patients with Cushing disease who had postsurgical remission and at least one follow-up visit with a pituitary expert and 92 patients with NFPA who were matched to patients with Cushing disease based on age and sex. The authors regarded autoimmune disease diagnosed within 36 months of the surgery to be temporally associated with Cushing disease remission. Among the autoimmune diseases considered were “rheumatoid arthritis, Sjögren syndrome, systemic lupus erythematosus, autoimmune thyroiditis, celiac disease, psoriasis, vitiligo, autoimmune neuropathy, multiple sclerosis, myasthenia gravis, and ulcerative colitis.”

Patients differed in average body mass index and tumor size, but family history of autoimmune disease was similar in both groups. Average BMI was 34.5 in the Cushing group and 29.5 in the NFPA group. Average tumor size was 5.7 mm in the Cushing group and 21.3 mm in the NFPA group.

Before surgery, 2.9% of patients with Cushing disease and 15.4% of patients with NFPA had central hypothyroidism, and 8% in the Cushing group and 56.8% in the NFPA group had hyperprolactinemia. Central adrenal insufficiency occurred in 11% with NFPA and in all with Cushing disease, by definition.

After surgery, 93.8% in the Cushing group and 16.5% in the NFPA group had adrenal insufficiency. In addition, patients with Cushing disease had lower postsurgical nadir serum cortisol levels (63.8 nmol/L) than those with NFPA (282.3 nmol/L).

Of the 17 patients with Cushing disease — all women — who developed autoimmune disease within 3 years, 6 had a personal history of autoimmune disease and 7 had a family history of it. In addition, 41.2% of them had adrenal insufficiency when they developed the new autoimmune disease. Among the diseases were six autoimmune thyroiditis cases, three Sjögren syndrome cases, and two autoimmune seronegative spondyloarthropathy.

Dr. Heaney said he found it interesting that more than half of the new autoimmune diseases in patients with Cushing disease were related to the thyroid. “In this kind of setting, where you have a patient who has been producing too much steroid over a period of time and then you take that away, it’s almost like you release a brake on the TSH [thyroid-stimulating hormone],” Dr. Heaney said. “So, there’s probably some rebound in TSH that occurs, and that could be driving the thyroiditis, to some extent, that we see in these patients.”

Only one patient with NFPA developed new-onset autoimmune disease, a woman who developed Graves disease 22 months after surgery. When the researchers excluded patients in both groups with central hypothyroidism, new-onset autoimmune disease was still significantly higher (11.4%) in the Cushing group than in the NFPA group (1.9%; HR, 7.02; 95% CI, 2.54-19.39).
 

Could Postoperative Adrenal Insufficiency Contribute to Risk?

Within the Cushing cohort, those who developed autoimmune disease had a lower BMI (31.8 vs 34.8) and larger tumor size (7.2 vs 5.6 mm) than those who didn’t develop new autoimmune disease. Patients who developed autoimmune disease also had a lower baseline urine free cortisol ratio (2.7 vs 6.3) before surgery and more family history of autoimmune disease (41.2% vs 20.9%) than those who didn’t develop one.

“The higher prevalence of adrenal insufficiency and the lower nadir serum cortisol levels in the Cushing disease group suggest that the postoperative adrenal insufficiency in the Cushing disease group might have contributed to autoimmune disease pathogenesis,” the authors wrote. “This finding is clinically significant because cortisol plays a pivotal role in modulating the immune system.”

Most postoperative management among patients with Cushing disease was similar, with all but one patient receiving 0.5 or 1 mg daily dexamethasone within the first week after surgery. (The one outlier received 5 mg daily prednisone.) However, fewer patients who developed autoimmune disease (17.6%) received supraphysiologic doses of glucocorticoid — equivalent to at least 25 mg hydrocortisone — compared with patients who didn’t develop autoimmune disease (41.8%).

“Although the daily average hydrocortisone equivalent replacement doses within the first month and during long-term follow-up were within the physiologic range in both subgroups, patients with Cushing disease who had autoimmune disease received slightly lower doses of glucocorticoid replacement within the first month after surgery,” the authors reported. “The immediate postoperative period might be a critical window where supraphysiologic glucocorticoids seem to be protective with regard to development of autoimmune disease,” they wrote, though they acknowledged the study’s retrospective design as a limitation in drawing that conclusion.

At the least, they suggested that new symptoms in patients with Cushing disease, particularly those with a family history of autoimmune disease, should prompt investigation of potential autoimmune disease.

Recordati Rare Diseases funded the study. The research was also conducted with support from Harvard Catalyst (the Harvard Clinical and Translational Science Center) as well as financial contributions from Harvard University and its affiliated academic healthcare centers. One author reported holding stocks in Pfizer and Amgen, and another reported receiving consulting fees from Corcept. Dr. Heaney reported receiving institutional grants for trials from Corcept, Ascendis, Crinetics, and Sparrow Pharm; serving on the advisory board for Xeris, Recordati, Corcept, Novo Nordisk, Lundbeck, and Crinetics; and serving as a speaker for Chiesi, Novo Nordisk, and Corcept.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Age older than 65 years and serum creatinine greater than 140 micromol/L at the time of systemic polyarteritis nodosa (PAN) diagnosis were significant predictors of mortality.

METHODOLOGY:

• A total of 358 patients diagnosed with PAN between 1990 and 2020 were identified from retrospective chart reviews and prospective cohorts from nine countries as a part of GLOBAL-PAN, a collaboration of the European Vasculitis Society, the Vasculitis Clinical Research Consortium, and other networks.
• The goal of the retrospective chart review was to characterize the nature, presentation, and survival rates of patients with PAN.
• The study population included 174 female and 184 male patients; 282 had systemic PAN (sPAN) and 76 had cutaneous PAN (cPAN); the mean age at diagnosis was 44.3 years.

TAKEAWAY:

• Overall survival rates at 1, 5, and 10 years for patients with sPAN were 97.1%, 94.0%, and 89.0%, respectively.
• Significant independent predictors of mortality were age ≥ 65 years at the time of sPAN diagnosis (hazard ratio [HR], 3.85), serum creatinine > 140 micromol/L at the time of diagnosis (HR, 4.93), gastrointestinal involvement (HR, 3.51), and central nervous system involvement (HR, 3.56).
• Constitutional symptoms were significantly more common in patients with sPAN vs cPAN (78.8% vs 44.7%), while patients with cPAN were significantly more likely to be female and have more skin nodules than patients with sPAN.
• Relapse over a median disease duration of 59.6 months was slightly higher for cPAN vs sPAN (38.8% vs 32.1%).

IN PRACTICE:

“This study helps better define the demographic and clinical characteristics of patients with PAN and differentiates sPAN from cPAN,” the researchers wrote.

SOURCE:

The lead author of the study was Omer Karadag, MD, of Hacettepe University, Ankara, Turkey. The study was published online on February 12 in Arthritis & Rheumatology.

LIMITATIONS:

Study limitations included the combination of prospective and retrospective data, varying approaches to patient assessment, and lack of data on treatment effects.

DISCLOSURES:

The study was supported by the Vasculitis Clinical Research Consortium, which received funding from the National Center for Advancing Translational Science, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the National Center for Research Resources. Dr. Karadag disclosed research grants from AbbVie, Novartis, Viela-Bio, and TR-Pharma, and consulting fees from AbbVie, Abdi Ibrahim, Celltrion, Novartis, Pfizer, Sandoz, and UCB.

A version of this article appeared on Medscape.com.

TOPLINE:

Age older than 65 years and serum creatinine greater than 140 micromol/L at the time of systemic polyarteritis nodosa (PAN) diagnosis were significant predictors of mortality.

METHODOLOGY:

• A total of 358 patients diagnosed with PAN between 1990 and 2020 were identified from retrospective chart reviews and prospective cohorts from nine countries as a part of GLOBAL-PAN, a collaboration of the European Vasculitis Society, the Vasculitis Clinical Research Consortium, and other networks.
• The goal of the retrospective chart review was to characterize the nature, presentation, and survival rates of patients with PAN.
• The study population included 174 female and 184 male patients; 282 had systemic PAN (sPAN) and 76 had cutaneous PAN (cPAN); the mean age at diagnosis was 44.3 years.

TAKEAWAY:

• Overall survival rates at 1, 5, and 10 years for patients with sPAN were 97.1%, 94.0%, and 89.0%, respectively.
• Significant independent predictors of mortality were age ≥ 65 years at the time of sPAN diagnosis (hazard ratio [HR], 3.85), serum creatinine > 140 micromol/L at the time of diagnosis (HR, 4.93), gastrointestinal involvement (HR, 3.51), and central nervous system involvement (HR, 3.56).
• Constitutional symptoms were significantly more common in patients with sPAN vs cPAN (78.8% vs 44.7%), while patients with cPAN were significantly more likely to be female and have more skin nodules than patients with sPAN.
• Relapse over a median disease duration of 59.6 months was slightly higher for cPAN vs sPAN (38.8% vs 32.1%).

IN PRACTICE:

“This study helps better define the demographic and clinical characteristics of patients with PAN and differentiates sPAN from cPAN,” the researchers wrote.

SOURCE:

The lead author of the study was Omer Karadag, MD, of Hacettepe University, Ankara, Turkey. The study was published online on February 12 in Arthritis & Rheumatology.

LIMITATIONS:

Study limitations included the combination of prospective and retrospective data, varying approaches to patient assessment, and lack of data on treatment effects.

DISCLOSURES:

The study was supported by the Vasculitis Clinical Research Consortium, which received funding from the National Center for Advancing Translational Science, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the National Center for Research Resources. Dr. Karadag disclosed research grants from AbbVie, Novartis, Viela-Bio, and TR-Pharma, and consulting fees from AbbVie, Abdi Ibrahim, Celltrion, Novartis, Pfizer, Sandoz, and UCB.

A version of this article appeared on Medscape.com.

TOPLINE:

Age older than 65 years and serum creatinine greater than 140 micromol/L at the time of systemic polyarteritis nodosa (PAN) diagnosis were significant predictors of mortality.

METHODOLOGY:

• A total of 358 patients diagnosed with PAN between 1990 and 2020 were identified from retrospective chart reviews and prospective cohorts from nine countries as a part of GLOBAL-PAN, a collaboration of the European Vasculitis Society, the Vasculitis Clinical Research Consortium, and other networks.
• The goal of the retrospective chart review was to characterize the nature, presentation, and survival rates of patients with PAN.
• The study population included 174 female and 184 male patients; 282 had systemic PAN (sPAN) and 76 had cutaneous PAN (cPAN); the mean age at diagnosis was 44.3 years.

TAKEAWAY:

• Overall survival rates at 1, 5, and 10 years for patients with sPAN were 97.1%, 94.0%, and 89.0%, respectively.
• Significant independent predictors of mortality were age ≥ 65 years at the time of sPAN diagnosis (hazard ratio [HR], 3.85), serum creatinine > 140 micromol/L at the time of diagnosis (HR, 4.93), gastrointestinal involvement (HR, 3.51), and central nervous system involvement (HR, 3.56).
• Constitutional symptoms were significantly more common in patients with sPAN vs cPAN (78.8% vs 44.7%), while patients with cPAN were significantly more likely to be female and have more skin nodules than patients with sPAN.
• Relapse over a median disease duration of 59.6 months was slightly higher for cPAN vs sPAN (38.8% vs 32.1%).

IN PRACTICE:

“This study helps better define the demographic and clinical characteristics of patients with PAN and differentiates sPAN from cPAN,” the researchers wrote.

SOURCE:

The lead author of the study was Omer Karadag, MD, of Hacettepe University, Ankara, Turkey. The study was published online on February 12 in Arthritis & Rheumatology.

LIMITATIONS:

Study limitations included the combination of prospective and retrospective data, varying approaches to patient assessment, and lack of data on treatment effects.

DISCLOSURES:

The study was supported by the Vasculitis Clinical Research Consortium, which received funding from the National Center for Advancing Translational Science, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the National Center for Research Resources. Dr. Karadag disclosed research grants from AbbVie, Novartis, Viela-Bio, and TR-Pharma, and consulting fees from AbbVie, Abdi Ibrahim, Celltrion, Novartis, Pfizer, Sandoz, and UCB.

A version of this article appeared on Medscape.com.

Postinfectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS) is a distinct, centrally mediated condition, with evidence of autonomic, immune, and metabolic dysfunction, new "deep phenotyping" data suggested.

The study was initiated in 2016 at the US National Institutes of Health. Its aim was to better elucidate the underlying pathophysiology of ME/CFS, a multisystem disorder characterized by persistent and disabling fatigue, post-exertional malaise, cognitive complaints, and other physical symptoms. A total of 17 carefully selected individuals with PI-ME/CFS onset within the prior 5 years were compared with 21 healthy volunteers on a more extensive set of biologic measurements than has been examined in any prior study of the condition.

Overall, the findings suggested that ME/CFS is “a distinct entity characterized by somatic and cognitive complaints that are centrally mediated,” with fatigue that is “defined by effort preferences and central autonomic dysfunction,” Brian T. Walitt, MD, of the National Institute of Neurological Disorders and Stroke (NINDS), Bethesda, Maryland, and colleagues wrote in the paper, published on February 21 in Nature Communications.

In addition, “there are distinct sex signatures of immune and metabolic dysregulation which suggest persistent antigenic stimulation.” Physical deconditioning over time, while not the source of the condition, “is an important consequence,” the authors added.

Asked to comment, Hector Bonilla, MD, director of the ME/CFS Clinic and codirector of the Stanford Post-Acute COVID-19 Syndrome Clinic, Atherton, California, pointed out that the sample was small and the study was cross-sectional and therefore likely missed dynamic changes in the patients.

Nonetheless, Dr. Bonilla told this news organization, “they have shown clear objective changes in patients with ME/CFS not seen in the controls. These are present in the microbiome, in the immune system, and in metabolites, especially in spinal fluid, that lead to a neuroinflammatory condition. And these are linked with autonomic dysfunction that can explain many of the symptoms that patients experience ... The symptoms are not manufactured by them.”

Thus far, the only treatments for ME/CFS are symptomatic. Understanding the pathophysiology is essential to identifying disease-modifying therapy, study lead author Avindra Nath, MD, Senior Investigator and Clinical Director of Intramural Research at NINDS, told this news organization.

“The disease is real. But our medical profession is limited in what they can do to diagnose or impact them ... The first thing we need to do is try to understand the pathophysiology. So that’s why the study was put together,” Dr. Nath said.

Postinfectious syndromes including ME/CFS have been given many names, including post-Lyme disease, Gulf War illness, and more recently, long COVID. With ME/CFS, the Epstein-Barr virus has historically been one of the most commonly associated triggers, although several other viral, bacterial, and environmental toxins have been implicated.

“There are a whole host of these things that have very similar symptoms or overlapping symptoms ... It’s quite possible that the underlying pathophysiology overlaps between all these syndromes,” Dr. Nath noted.

Another ME/CFS expert not involved in the study, researcher Michael VanElzakker, PhD, of the Neurotherapeutics Division at Harvard Medical School and Massachusetts General Hospital, Boston, said that the possibility of antigen persistence of the infectious pathogen arising from the immune system profiling conducted in the study is noteworthy and merits further study.

“To me, the obvious next step would be techniques like tissue-based assays and T-cell sequencing to try and understand what exactly those antigens are and what their source might be. Importantly, it is probably not the same antigen or pathogen source in all patients, but that’s a question that needs an answer,” Dr. VanElzakker said.

Of note, the 17 study participants had been adjudicated by an expert panel from an initial 484 inquiries and 217 who underwent detailed case reviews. They had to meet at least one of three published ME/CFS criteria and to have moderate to severe clinical symptom severity as determined by several fatigue scores. None met the criteria for psychiatric diagnoses.

Yet, even in the cases that met study criteria, underlying causes emerged in 20% of the participants over time, suggesting diagnostic misattribution. “This misclassification bias has important ramifications on the interpretation of the existing ME/CFS research literature,” the authors wrote.

Dr. VanElzakker noted, “The fact that this research study was probably the most detailed workup many of these patients had ever gotten is a serious indictment of our current profit-based healthcare system’s prioritization of 15-minute doctor’s appointments. It is almost certain that other patients would also benefit from an intensive detailed workup.”
 

Multiple Abnormalities Identified

There were no differences between the PI-ME/CFS and control groups in ventilatory function, muscle oxygenation, mechanical efficiency, resting energy expenditure, basal mitochondrial function of immune cells, muscle fiber composition, or body composition, suggesting the absence of a resting low-energy state, the authors said.

In 40-minute head-up tilt-table testing, there were no differences between the ME/CFS and control groups in frequency or orthostatic hypotension or extensive orthostatic tachycardia. However, a 24-hour ambulatory electrocardiogram showed that the patients with PI-ME/CFS had diminished heart rate variability. They also showed increased heart rate throughout the day, suggesting increased sympathetic activity, and a diminished drop in nighttime heart rate, suggesting decreased parasympathetic activity.

“Considered together, these data suggest that there is an alteration in autonomic tone, implying central nervous system regulatory change,” Dr. Walitt and colleagues wrote.

On the “Effort-Expenditure for Rewards Task,” the participants with PI-ME/CFS showed significant differences in “effort preference,” or a tendency to avoid the harder tasks, as well as a slowing of button-pushing over time, compared with the controls, even with easier tasks. This pattern suggests that those with PI-ME/CFS were “pacing to limit exertion and associated feelings of discomfort,” the authors wrote.

Dr. Nath describes this behavior as akin to “if you develop a flu, you feel that you just want to lay down in bed and not hurt yourself. It’s not that you’re not capable of doing [the task], but your body tells you don’t do it. Your body just wants to fight the infection ... these people just never bounce back.”

Compared with the controls, the participants with PI-ME/CFS failed to maintain a moderate grip force even though there was no difference in maximum grip strength or arm muscle mass. This performance difference correlated with decreased activity of the right temporal-parietal junction, a novel observation suggesting that the fatigue in the PI-ME/CFS group “is due to dysfunction of integrative brain regions that drive the motor cortex, the cause of which needs to be further explored,” Dr. Walitt and colleagues wrote.

On cardiopulmonary testing, peak power, peak respiratory rate, peak heart rate, and peak VO₂ were all lower in the PI-ME/CFS group, correlating to a difference of approximately 3.3 metabolic equivalent of task units. The differential cardiorespiratory performance relates to “autonomic function, hypothalamic-pituitary-adrenal axis hyporesponsiveness, and muscular deconditioning from disuse that clinically impacts activities of daily life,” they said.

In the participants with PI-ME/CFS, catechol levels in cerebrospinal fluid correlated with grip strength and effort preference, and several metabolites of the dopamine pathway correlated with several cognitive symptoms.

“This suggests that central nervous system catechol pathways are dysregulated in PI-ME/CFS and may play a role in effort preference and cognitive complaints,” as well as decreased central catecholamine biosynthesis. Similar findings have been seen in patients with long COVID, the authors noted.

There were increased naive B cells and decreased switched memory B cells in blood of participants with PI-ME/CFS. Contrary to prior studies, there was no consistent pattern of autoimmunity across all participants with PI-ME/CFS, and no previously undescribed antibodies were identified.

However, programmed cell death protein 1, a marker of T-cell exhaustion and activation, was elevated in the cerebrospinal fluid of the patients with PI-ME/CFS.

Several sex-based differences were noted, including in immune cell expression in cerebrospinal fluid, peripheral blood mononuclear cell gene expression, and muscle gene expression. Males and females also differed in the cerebrospinal metabolomics that distinguished the participants with PI-ME/CFS from controls.
 

What Do These Findings Suggest About Treatment?

The data point to several treatment implications. For one, the finding of possible immune exhaustion suggests that immune checkpoint inhibitors may be therapeutic by promoting clearance of foreign antigens. Immune dysfunction leads to neurochemical alterations that affect neuronal circuits, which may be another point of intervention, the authors suggested.

On the other hand, “attempting to target downstream mechanisms with exercise, cognitive behavioral therapy, or autonomic directed therapies may have limited impact on symptom burden, as it would not address the root cause of PI-ME/CFS,” they noted.

Combination therapy targeting multiple pathways along with a personalized medicine approach should be considered, they said.

“I think the most important thing is not to discount these patients,” Dr. Nath told this news organization. “They have a real disease, and we need to be empathetic towards them. We also need to make sure that they don’t have something underlying that is treatable, and then treat them symptomatically the best that you can. If not, then refer them to ME/CFS studies or clinics where people specialize in these conditions and work with them.”

The study authors and Dr. VanElzakker reported no relevant financial relationships. Dr. Bonilla consults for United Health and Resverlogix.
 

A version of this article appeared on Medscape.com.

Postinfectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS) is a distinct, centrally mediated condition, with evidence of autonomic, immune, and metabolic dysfunction, new "deep phenotyping" data suggested.

The study was initiated in 2016 at the US National Institutes of Health. Its aim was to better elucidate the underlying pathophysiology of ME/CFS, a multisystem disorder characterized by persistent and disabling fatigue, post-exertional malaise, cognitive complaints, and other physical symptoms. A total of 17 carefully selected individuals with PI-ME/CFS onset within the prior 5 years were compared with 21 healthy volunteers on a more extensive set of biologic measurements than has been examined in any prior study of the condition.

Overall, the findings suggested that ME/CFS is “a distinct entity characterized by somatic and cognitive complaints that are centrally mediated,” with fatigue that is “defined by effort preferences and central autonomic dysfunction,” Brian T. Walitt, MD, of the National Institute of Neurological Disorders and Stroke (NINDS), Bethesda, Maryland, and colleagues wrote in the paper, published on February 21 in Nature Communications.

In addition, “there are distinct sex signatures of immune and metabolic dysregulation which suggest persistent antigenic stimulation.” Physical deconditioning over time, while not the source of the condition, “is an important consequence,” the authors added.

Asked to comment, Hector Bonilla, MD, director of the ME/CFS Clinic and codirector of the Stanford Post-Acute COVID-19 Syndrome Clinic, Atherton, California, pointed out that the sample was small and the study was cross-sectional and therefore likely missed dynamic changes in the patients.

Nonetheless, Dr. Bonilla told this news organization, “they have shown clear objective changes in patients with ME/CFS not seen in the controls. These are present in the microbiome, in the immune system, and in metabolites, especially in spinal fluid, that lead to a neuroinflammatory condition. And these are linked with autonomic dysfunction that can explain many of the symptoms that patients experience ... The symptoms are not manufactured by them.”

Thus far, the only treatments for ME/CFS are symptomatic. Understanding the pathophysiology is essential to identifying disease-modifying therapy, study lead author Avindra Nath, MD, Senior Investigator and Clinical Director of Intramural Research at NINDS, told this news organization.

“The disease is real. But our medical profession is limited in what they can do to diagnose or impact them ... The first thing we need to do is try to understand the pathophysiology. So that’s why the study was put together,” Dr. Nath said.

Postinfectious syndromes including ME/CFS have been given many names, including post-Lyme disease, Gulf War illness, and more recently, long COVID. With ME/CFS, the Epstein-Barr virus has historically been one of the most commonly associated triggers, although several other viral, bacterial, and environmental toxins have been implicated.

“There are a whole host of these things that have very similar symptoms or overlapping symptoms ... It’s quite possible that the underlying pathophysiology overlaps between all these syndromes,” Dr. Nath noted.

Another ME/CFS expert not involved in the study, researcher Michael VanElzakker, PhD, of the Neurotherapeutics Division at Harvard Medical School and Massachusetts General Hospital, Boston, said that the possibility of antigen persistence of the infectious pathogen arising from the immune system profiling conducted in the study is noteworthy and merits further study.

“To me, the obvious next step would be techniques like tissue-based assays and T-cell sequencing to try and understand what exactly those antigens are and what their source might be. Importantly, it is probably not the same antigen or pathogen source in all patients, but that’s a question that needs an answer,” Dr. VanElzakker said.

Of note, the 17 study participants had been adjudicated by an expert panel from an initial 484 inquiries and 217 who underwent detailed case reviews. They had to meet at least one of three published ME/CFS criteria and to have moderate to severe clinical symptom severity as determined by several fatigue scores. None met the criteria for psychiatric diagnoses.

Yet, even in the cases that met study criteria, underlying causes emerged in 20% of the participants over time, suggesting diagnostic misattribution. “This misclassification bias has important ramifications on the interpretation of the existing ME/CFS research literature,” the authors wrote.

Dr. VanElzakker noted, “The fact that this research study was probably the most detailed workup many of these patients had ever gotten is a serious indictment of our current profit-based healthcare system’s prioritization of 15-minute doctor’s appointments. It is almost certain that other patients would also benefit from an intensive detailed workup.”
 

Multiple Abnormalities Identified

There were no differences between the PI-ME/CFS and control groups in ventilatory function, muscle oxygenation, mechanical efficiency, resting energy expenditure, basal mitochondrial function of immune cells, muscle fiber composition, or body composition, suggesting the absence of a resting low-energy state, the authors said.

In 40-minute head-up tilt-table testing, there were no differences between the ME/CFS and control groups in frequency or orthostatic hypotension or extensive orthostatic tachycardia. However, a 24-hour ambulatory electrocardiogram showed that the patients with PI-ME/CFS had diminished heart rate variability. They also showed increased heart rate throughout the day, suggesting increased sympathetic activity, and a diminished drop in nighttime heart rate, suggesting decreased parasympathetic activity.

“Considered together, these data suggest that there is an alteration in autonomic tone, implying central nervous system regulatory change,” Dr. Walitt and colleagues wrote.

On the “Effort-Expenditure for Rewards Task,” the participants with PI-ME/CFS showed significant differences in “effort preference,” or a tendency to avoid the harder tasks, as well as a slowing of button-pushing over time, compared with the controls, even with easier tasks. This pattern suggests that those with PI-ME/CFS were “pacing to limit exertion and associated feelings of discomfort,” the authors wrote.

Dr. Nath describes this behavior as akin to “if you develop a flu, you feel that you just want to lay down in bed and not hurt yourself. It’s not that you’re not capable of doing [the task], but your body tells you don’t do it. Your body just wants to fight the infection ... these people just never bounce back.”

Compared with the controls, the participants with PI-ME/CFS failed to maintain a moderate grip force even though there was no difference in maximum grip strength or arm muscle mass. This performance difference correlated with decreased activity of the right temporal-parietal junction, a novel observation suggesting that the fatigue in the PI-ME/CFS group “is due to dysfunction of integrative brain regions that drive the motor cortex, the cause of which needs to be further explored,” Dr. Walitt and colleagues wrote.

On cardiopulmonary testing, peak power, peak respiratory rate, peak heart rate, and peak VO₂ were all lower in the PI-ME/CFS group, correlating to a difference of approximately 3.3 metabolic equivalent of task units. The differential cardiorespiratory performance relates to “autonomic function, hypothalamic-pituitary-adrenal axis hyporesponsiveness, and muscular deconditioning from disuse that clinically impacts activities of daily life,” they said.

In the participants with PI-ME/CFS, catechol levels in cerebrospinal fluid correlated with grip strength and effort preference, and several metabolites of the dopamine pathway correlated with several cognitive symptoms.

“This suggests that central nervous system catechol pathways are dysregulated in PI-ME/CFS and may play a role in effort preference and cognitive complaints,” as well as decreased central catecholamine biosynthesis. Similar findings have been seen in patients with long COVID, the authors noted.

There were increased naive B cells and decreased switched memory B cells in blood of participants with PI-ME/CFS. Contrary to prior studies, there was no consistent pattern of autoimmunity across all participants with PI-ME/CFS, and no previously undescribed antibodies were identified.

However, programmed cell death protein 1, a marker of T-cell exhaustion and activation, was elevated in the cerebrospinal fluid of the patients with PI-ME/CFS.

Several sex-based differences were noted, including in immune cell expression in cerebrospinal fluid, peripheral blood mononuclear cell gene expression, and muscle gene expression. Males and females also differed in the cerebrospinal metabolomics that distinguished the participants with PI-ME/CFS from controls.
 

What Do These Findings Suggest About Treatment?

The data point to several treatment implications. For one, the finding of possible immune exhaustion suggests that immune checkpoint inhibitors may be therapeutic by promoting clearance of foreign antigens. Immune dysfunction leads to neurochemical alterations that affect neuronal circuits, which may be another point of intervention, the authors suggested.

On the other hand, “attempting to target downstream mechanisms with exercise, cognitive behavioral therapy, or autonomic directed therapies may have limited impact on symptom burden, as it would not address the root cause of PI-ME/CFS,” they noted.

Combination therapy targeting multiple pathways along with a personalized medicine approach should be considered, they said.

“I think the most important thing is not to discount these patients,” Dr. Nath told this news organization. “They have a real disease, and we need to be empathetic towards them. We also need to make sure that they don’t have something underlying that is treatable, and then treat them symptomatically the best that you can. If not, then refer them to ME/CFS studies or clinics where people specialize in these conditions and work with them.”

The study authors and Dr. VanElzakker reported no relevant financial relationships. Dr. Bonilla consults for United Health and Resverlogix.
 

A version of this article appeared on Medscape.com.

Postinfectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS) is a distinct, centrally mediated condition, with evidence of autonomic, immune, and metabolic dysfunction, new "deep phenotyping" data suggested.

The study was initiated in 2016 at the US National Institutes of Health. Its aim was to better elucidate the underlying pathophysiology of ME/CFS, a multisystem disorder characterized by persistent and disabling fatigue, post-exertional malaise, cognitive complaints, and other physical symptoms. A total of 17 carefully selected individuals with PI-ME/CFS onset within the prior 5 years were compared with 21 healthy volunteers on a more extensive set of biologic measurements than has been examined in any prior study of the condition.

Overall, the findings suggested that ME/CFS is “a distinct entity characterized by somatic and cognitive complaints that are centrally mediated,” with fatigue that is “defined by effort preferences and central autonomic dysfunction,” Brian T. Walitt, MD, of the National Institute of Neurological Disorders and Stroke (NINDS), Bethesda, Maryland, and colleagues wrote in the paper, published on February 21 in Nature Communications.

In addition, “there are distinct sex signatures of immune and metabolic dysregulation which suggest persistent antigenic stimulation.” Physical deconditioning over time, while not the source of the condition, “is an important consequence,” the authors added.

Asked to comment, Hector Bonilla, MD, director of the ME/CFS Clinic and codirector of the Stanford Post-Acute COVID-19 Syndrome Clinic, Atherton, California, pointed out that the sample was small and the study was cross-sectional and therefore likely missed dynamic changes in the patients.

Nonetheless, Dr. Bonilla told this news organization, “they have shown clear objective changes in patients with ME/CFS not seen in the controls. These are present in the microbiome, in the immune system, and in metabolites, especially in spinal fluid, that lead to a neuroinflammatory condition. And these are linked with autonomic dysfunction that can explain many of the symptoms that patients experience ... The symptoms are not manufactured by them.”

Thus far, the only treatments for ME/CFS are symptomatic. Understanding the pathophysiology is essential to identifying disease-modifying therapy, study lead author Avindra Nath, MD, Senior Investigator and Clinical Director of Intramural Research at NINDS, told this news organization.

“The disease is real. But our medical profession is limited in what they can do to diagnose or impact them ... The first thing we need to do is try to understand the pathophysiology. So that’s why the study was put together,” Dr. Nath said.

Postinfectious syndromes including ME/CFS have been given many names, including post-Lyme disease, Gulf War illness, and more recently, long COVID. With ME/CFS, the Epstein-Barr virus has historically been one of the most commonly associated triggers, although several other viral, bacterial, and environmental toxins have been implicated.

“There are a whole host of these things that have very similar symptoms or overlapping symptoms ... It’s quite possible that the underlying pathophysiology overlaps between all these syndromes,” Dr. Nath noted.

Another ME/CFS expert not involved in the study, researcher Michael VanElzakker, PhD, of the Neurotherapeutics Division at Harvard Medical School and Massachusetts General Hospital, Boston, said that the possibility of antigen persistence of the infectious pathogen arising from the immune system profiling conducted in the study is noteworthy and merits further study.

“To me, the obvious next step would be techniques like tissue-based assays and T-cell sequencing to try and understand what exactly those antigens are and what their source might be. Importantly, it is probably not the same antigen or pathogen source in all patients, but that’s a question that needs an answer,” Dr. VanElzakker said.

Of note, the 17 study participants had been adjudicated by an expert panel from an initial 484 inquiries and 217 who underwent detailed case reviews. They had to meet at least one of three published ME/CFS criteria and to have moderate to severe clinical symptom severity as determined by several fatigue scores. None met the criteria for psychiatric diagnoses.

Yet, even in the cases that met study criteria, underlying causes emerged in 20% of the participants over time, suggesting diagnostic misattribution. “This misclassification bias has important ramifications on the interpretation of the existing ME/CFS research literature,” the authors wrote.

Dr. VanElzakker noted, “The fact that this research study was probably the most detailed workup many of these patients had ever gotten is a serious indictment of our current profit-based healthcare system’s prioritization of 15-minute doctor’s appointments. It is almost certain that other patients would also benefit from an intensive detailed workup.”
 

Multiple Abnormalities Identified

There were no differences between the PI-ME/CFS and control groups in ventilatory function, muscle oxygenation, mechanical efficiency, resting energy expenditure, basal mitochondrial function of immune cells, muscle fiber composition, or body composition, suggesting the absence of a resting low-energy state, the authors said.

In 40-minute head-up tilt-table testing, there were no differences between the ME/CFS and control groups in frequency or orthostatic hypotension or extensive orthostatic tachycardia. However, a 24-hour ambulatory electrocardiogram showed that the patients with PI-ME/CFS had diminished heart rate variability. They also showed increased heart rate throughout the day, suggesting increased sympathetic activity, and a diminished drop in nighttime heart rate, suggesting decreased parasympathetic activity.

“Considered together, these data suggest that there is an alteration in autonomic tone, implying central nervous system regulatory change,” Dr. Walitt and colleagues wrote.

On the “Effort-Expenditure for Rewards Task,” the participants with PI-ME/CFS showed significant differences in “effort preference,” or a tendency to avoid the harder tasks, as well as a slowing of button-pushing over time, compared with the controls, even with easier tasks. This pattern suggests that those with PI-ME/CFS were “pacing to limit exertion and associated feelings of discomfort,” the authors wrote.

Dr. Nath describes this behavior as akin to “if you develop a flu, you feel that you just want to lay down in bed and not hurt yourself. It’s not that you’re not capable of doing [the task], but your body tells you don’t do it. Your body just wants to fight the infection ... these people just never bounce back.”

Compared with the controls, the participants with PI-ME/CFS failed to maintain a moderate grip force even though there was no difference in maximum grip strength or arm muscle mass. This performance difference correlated with decreased activity of the right temporal-parietal junction, a novel observation suggesting that the fatigue in the PI-ME/CFS group “is due to dysfunction of integrative brain regions that drive the motor cortex, the cause of which needs to be further explored,” Dr. Walitt and colleagues wrote.

On cardiopulmonary testing, peak power, peak respiratory rate, peak heart rate, and peak VO₂ were all lower in the PI-ME/CFS group, correlating to a difference of approximately 3.3 metabolic equivalent of task units. The differential cardiorespiratory performance relates to “autonomic function, hypothalamic-pituitary-adrenal axis hyporesponsiveness, and muscular deconditioning from disuse that clinically impacts activities of daily life,” they said.

In the participants with PI-ME/CFS, catechol levels in cerebrospinal fluid correlated with grip strength and effort preference, and several metabolites of the dopamine pathway correlated with several cognitive symptoms.

“This suggests that central nervous system catechol pathways are dysregulated in PI-ME/CFS and may play a role in effort preference and cognitive complaints,” as well as decreased central catecholamine biosynthesis. Similar findings have been seen in patients with long COVID, the authors noted.

There were increased naive B cells and decreased switched memory B cells in blood of participants with PI-ME/CFS. Contrary to prior studies, there was no consistent pattern of autoimmunity across all participants with PI-ME/CFS, and no previously undescribed antibodies were identified.

However, programmed cell death protein 1, a marker of T-cell exhaustion and activation, was elevated in the cerebrospinal fluid of the patients with PI-ME/CFS.

Several sex-based differences were noted, including in immune cell expression in cerebrospinal fluid, peripheral blood mononuclear cell gene expression, and muscle gene expression. Males and females also differed in the cerebrospinal metabolomics that distinguished the participants with PI-ME/CFS from controls.
 

What Do These Findings Suggest About Treatment?

The data point to several treatment implications. For one, the finding of possible immune exhaustion suggests that immune checkpoint inhibitors may be therapeutic by promoting clearance of foreign antigens. Immune dysfunction leads to neurochemical alterations that affect neuronal circuits, which may be another point of intervention, the authors suggested.

On the other hand, “attempting to target downstream mechanisms with exercise, cognitive behavioral therapy, or autonomic directed therapies may have limited impact on symptom burden, as it would not address the root cause of PI-ME/CFS,” they noted.

Combination therapy targeting multiple pathways along with a personalized medicine approach should be considered, they said.

“I think the most important thing is not to discount these patients,” Dr. Nath told this news organization. “They have a real disease, and we need to be empathetic towards them. We also need to make sure that they don’t have something underlying that is treatable, and then treat them symptomatically the best that you can. If not, then refer them to ME/CFS studies or clinics where people specialize in these conditions and work with them.”

The study authors and Dr. VanElzakker reported no relevant financial relationships. Dr. Bonilla consults for United Health and Resverlogix.
 

A version of this article appeared on Medscape.com.

Poor communication between physician and patient can cause a lot of harm, according to Joseph N. Cappella, PhD, Gerald R. Miller Professor Emeritus of Communication at the University of Pennsylvania in Philadelphia, and Richard N. Street Jr, PhD, professor of communication and media science at Texas A&M University in Houston, Texas. When a physician and patient talk past each other, it may impair the patient’s compliance with preventive measures, screening, and treatment; undermine the physician-patient relationship; exacerbate fears and concerns; and possibly lead patients to rely on misleading, incomplete, or simply incorrect information, turning away from evidence-based medicine.

Drs. Cappella and Street made these points in an essay recently published in JAMA. The essay marks the beginning of the JAMA series Communicating Medicine.

“Helping clinicians deliver accurate information more effectively can lead to better-informed patients,” wrote Anne R. Cappola, MD, professor of endocrinology, diabetes, and metabolism at the University of Pennsylvania, and Kirsten Bibbins-Domingo, MD, PhD, professor of medicine at the University of California, San Francisco, in an accompanying editorial. Drs. Cappola and Bibbins-Domingo also are editors of JAMA.

To establish a common understanding between physician and patient, Drs. Cappella and Street identified the following four responsibilities of the physician:

• Discover what the patient understands and why
• Provide accurate information in an understandable manner
• Promote the credibility of the information
• Verify whether the patient has understood.

“Research has shown that although medical facts need to be the basis for the clinician’s core message, those facts are more effectively communicated in a patient-clinician relationship characterized by trust and cooperation and when the information is presented in a manner that fosters patient understanding,” wrote Drs. Cappella and Street. This approach includes using interpreters for patients who do not fluently speak the physician’s language and supplementing explanations with simple written information, images, and videos.

Patients generally believe their physician’s information, and most patients view their physicians as a trustworthy source. Trust is based on the belief that the physician has the patient’s best interests at heart.

However, patients may be distrustful of their physician’s information if it contradicts their own belief system or personal experiences or because they inherently distrust the medical profession.

In addition, patients are less willing to accept explanations and recommendations if they feel misunderstood, judged, discriminated against, or rushed by the physician. The basis for effective communication is a relationship with patients that is built on trust and respect. Empirically supported strategies for expressing respect and building trust include the following:

• Affirming the patient’s values
• Anticipating and addressing false or misleading information
• Using simple, jargon-free language
• Embedding facts into a story, rather than presenting the scientific evidence dryly.

“Conveying factual material using these techniques makes facts more engaging and memorable,” wrote Drs. Cappella and Street. It is crucial to inquire about and consider the patient’s perspective, health beliefs, assumptions, concerns, needs, and stories in the conversation.

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Poor communication between physician and patient can cause a lot of harm, according to Joseph N. Cappella, PhD, Gerald R. Miller Professor Emeritus of Communication at the University of Pennsylvania in Philadelphia, and Richard N. Street Jr, PhD, professor of communication and media science at Texas A&M University in Houston, Texas. When a physician and patient talk past each other, it may impair the patient’s compliance with preventive measures, screening, and treatment; undermine the physician-patient relationship; exacerbate fears and concerns; and possibly lead patients to rely on misleading, incomplete, or simply incorrect information, turning away from evidence-based medicine.

Drs. Cappella and Street made these points in an essay recently published in JAMA. The essay marks the beginning of the JAMA series Communicating Medicine.

“Helping clinicians deliver accurate information more effectively can lead to better-informed patients,” wrote Anne R. Cappola, MD, professor of endocrinology, diabetes, and metabolism at the University of Pennsylvania, and Kirsten Bibbins-Domingo, MD, PhD, professor of medicine at the University of California, San Francisco, in an accompanying editorial. Drs. Cappola and Bibbins-Domingo also are editors of JAMA.

To establish a common understanding between physician and patient, Drs. Cappella and Street identified the following four responsibilities of the physician:

• Discover what the patient understands and why
• Provide accurate information in an understandable manner
• Promote the credibility of the information
• Verify whether the patient has understood.

“Research has shown that although medical facts need to be the basis for the clinician’s core message, those facts are more effectively communicated in a patient-clinician relationship characterized by trust and cooperation and when the information is presented in a manner that fosters patient understanding,” wrote Drs. Cappella and Street. This approach includes using interpreters for patients who do not fluently speak the physician’s language and supplementing explanations with simple written information, images, and videos.

Patients generally believe their physician’s information, and most patients view their physicians as a trustworthy source. Trust is based on the belief that the physician has the patient’s best interests at heart.

However, patients may be distrustful of their physician’s information if it contradicts their own belief system or personal experiences or because they inherently distrust the medical profession.

In addition, patients are less willing to accept explanations and recommendations if they feel misunderstood, judged, discriminated against, or rushed by the physician. The basis for effective communication is a relationship with patients that is built on trust and respect. Empirically supported strategies for expressing respect and building trust include the following:

• Affirming the patient’s values
• Anticipating and addressing false or misleading information
• Using simple, jargon-free language
• Embedding facts into a story, rather than presenting the scientific evidence dryly.

“Conveying factual material using these techniques makes facts more engaging and memorable,” wrote Drs. Cappella and Street. It is crucial to inquire about and consider the patient’s perspective, health beliefs, assumptions, concerns, needs, and stories in the conversation.

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Poor communication between physician and patient can cause a lot of harm, according to Joseph N. Cappella, PhD, Gerald R. Miller Professor Emeritus of Communication at the University of Pennsylvania in Philadelphia, and Richard N. Street Jr, PhD, professor of communication and media science at Texas A&M University in Houston, Texas. When a physician and patient talk past each other, it may impair the patient’s compliance with preventive measures, screening, and treatment; undermine the physician-patient relationship; exacerbate fears and concerns; and possibly lead patients to rely on misleading, incomplete, or simply incorrect information, turning away from evidence-based medicine.

Drs. Cappella and Street made these points in an essay recently published in JAMA. The essay marks the beginning of the JAMA series Communicating Medicine.

“Helping clinicians deliver accurate information more effectively can lead to better-informed patients,” wrote Anne R. Cappola, MD, professor of endocrinology, diabetes, and metabolism at the University of Pennsylvania, and Kirsten Bibbins-Domingo, MD, PhD, professor of medicine at the University of California, San Francisco, in an accompanying editorial. Drs. Cappola and Bibbins-Domingo also are editors of JAMA.

To establish a common understanding between physician and patient, Drs. Cappella and Street identified the following four responsibilities of the physician:

• Discover what the patient understands and why
• Provide accurate information in an understandable manner
• Promote the credibility of the information
• Verify whether the patient has understood.

“Research has shown that although medical facts need to be the basis for the clinician’s core message, those facts are more effectively communicated in a patient-clinician relationship characterized by trust and cooperation and when the information is presented in a manner that fosters patient understanding,” wrote Drs. Cappella and Street. This approach includes using interpreters for patients who do not fluently speak the physician’s language and supplementing explanations with simple written information, images, and videos.

Patients generally believe their physician’s information, and most patients view their physicians as a trustworthy source. Trust is based on the belief that the physician has the patient’s best interests at heart.

However, patients may be distrustful of their physician’s information if it contradicts their own belief system or personal experiences or because they inherently distrust the medical profession.

In addition, patients are less willing to accept explanations and recommendations if they feel misunderstood, judged, discriminated against, or rushed by the physician. The basis for effective communication is a relationship with patients that is built on trust and respect. Empirically supported strategies for expressing respect and building trust include the following:

• Affirming the patient’s values
• Anticipating and addressing false or misleading information
• Using simple, jargon-free language
• Embedding facts into a story, rather than presenting the scientific evidence dryly.

“Conveying factual material using these techniques makes facts more engaging and memorable,” wrote Drs. Cappella and Street. It is crucial to inquire about and consider the patient’s perspective, health beliefs, assumptions, concerns, needs, and stories in the conversation.

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Inflammatory arthritis (IA) occurred in one-third of patients with systemic sclerosis (SSc) in a large observational study and was significantly associated with poor quality of life and physical function, as well as diffuse disease, musculoskeletal manifestations, myositis, and sicca.

METHODOLOGY:

• Researchers reviewed data from 1717 adults with SSc who were enrolled in the Australian  Cohort Study to identify those with IA, defined as the presence of synovitis in one or more joints on clinical examination documented by the treating physician.
• The primary outcome was health-related quality of life (HRQoL) based on patient reports using the Medical Outcomes Short Form 36 and Patient-Reported Outcomes Measurement Information System, and physical function measured with the Health Assessment Questionnaire.

TAKEAWAY:

• IA was identified in 33.3% of the study participants over a median of 4.3 years’ follow-up. IA occurred at a median age of about 60 years and after a median SSc disease duration of 7.9 years. No significant differences in baseline demographics appeared between patients with and without IA.
• Patients with IA had significantly increased risk for diffuse cutaneous SSc (odds ratio [OR], 1.33), concurrent musculoskeletal manifestations such as tendon friction rubs and joint contractures (OR, 1.70), myositis (OR, 2.11), and sicca symptoms (OR, 1.57), compared with those without.
• Patients with IA reported significantly lower HRQoL scores and significantly greater physical disability, compared with those who did not have IA (P < .001 for both).
• IA was significantly less common among patients with , compared with those without pulmonary arterial hypertension (7.2% vs 11.3%; P = .007).

IN PRACTICE:

“Recognizing the presence of IA in SSc is an important first step, as its treatment and monitoring may alleviate some of the associated morbidity,” the researchers wrote.

SOURCE:

The lead author of the study was Eric Schwender, a medical student at the Royal College of Surgeons in Ireland, Dublin, Ireland. The study was published online in Arthritis Care & Research.

LIMITATIONS:

The inability to assess distribution and severity of IA limited the results, as did the inability to assess the impact of disease-modifying antirheumatic drugs in patients with IA.

DISCLOSURES:

The study was supported by Scleroderma Australia, Arthritis Australia, Actelion Australia, Bayer, CSL Biotherapies, GlaxoSmithKline Australia, and Pfizer, as well as grants to several researchers from the National Health and Medical Research Council of Australia. Lead author Mr. Schwender had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

Inflammatory arthritis (IA) occurred in one-third of patients with systemic sclerosis (SSc) in a large observational study and was significantly associated with poor quality of life and physical function, as well as diffuse disease, musculoskeletal manifestations, myositis, and sicca.

METHODOLOGY:

• Researchers reviewed data from 1717 adults with SSc who were enrolled in the Australian  Cohort Study to identify those with IA, defined as the presence of synovitis in one or more joints on clinical examination documented by the treating physician.
• The primary outcome was health-related quality of life (HRQoL) based on patient reports using the Medical Outcomes Short Form 36 and Patient-Reported Outcomes Measurement Information System, and physical function measured with the Health Assessment Questionnaire.

TAKEAWAY:

• IA was identified in 33.3% of the study participants over a median of 4.3 years’ follow-up. IA occurred at a median age of about 60 years and after a median SSc disease duration of 7.9 years. No significant differences in baseline demographics appeared between patients with and without IA.
• Patients with IA had significantly increased risk for diffuse cutaneous SSc (odds ratio [OR], 1.33), concurrent musculoskeletal manifestations such as tendon friction rubs and joint contractures (OR, 1.70), myositis (OR, 2.11), and sicca symptoms (OR, 1.57), compared with those without.
• Patients with IA reported significantly lower HRQoL scores and significantly greater physical disability, compared with those who did not have IA (P < .001 for both).
• IA was significantly less common among patients with , compared with those without pulmonary arterial hypertension (7.2% vs 11.3%; P = .007).

IN PRACTICE:

“Recognizing the presence of IA in SSc is an important first step, as its treatment and monitoring may alleviate some of the associated morbidity,” the researchers wrote.

SOURCE:

The lead author of the study was Eric Schwender, a medical student at the Royal College of Surgeons in Ireland, Dublin, Ireland. The study was published online in Arthritis Care & Research.

LIMITATIONS:

The inability to assess distribution and severity of IA limited the results, as did the inability to assess the impact of disease-modifying antirheumatic drugs in patients with IA.

DISCLOSURES:

The study was supported by Scleroderma Australia, Arthritis Australia, Actelion Australia, Bayer, CSL Biotherapies, GlaxoSmithKline Australia, and Pfizer, as well as grants to several researchers from the National Health and Medical Research Council of Australia. Lead author Mr. Schwender had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

Inflammatory arthritis (IA) occurred in one-third of patients with systemic sclerosis (SSc) in a large observational study and was significantly associated with poor quality of life and physical function, as well as diffuse disease, musculoskeletal manifestations, myositis, and sicca.

METHODOLOGY:

• Researchers reviewed data from 1717 adults with SSc who were enrolled in the Australian  Cohort Study to identify those with IA, defined as the presence of synovitis in one or more joints on clinical examination documented by the treating physician.
• The primary outcome was health-related quality of life (HRQoL) based on patient reports using the Medical Outcomes Short Form 36 and Patient-Reported Outcomes Measurement Information System, and physical function measured with the Health Assessment Questionnaire.

TAKEAWAY:

• IA was identified in 33.3% of the study participants over a median of 4.3 years’ follow-up. IA occurred at a median age of about 60 years and after a median SSc disease duration of 7.9 years. No significant differences in baseline demographics appeared between patients with and without IA.
• Patients with IA had significantly increased risk for diffuse cutaneous SSc (odds ratio [OR], 1.33), concurrent musculoskeletal manifestations such as tendon friction rubs and joint contractures (OR, 1.70), myositis (OR, 2.11), and sicca symptoms (OR, 1.57), compared with those without.
• Patients with IA reported significantly lower HRQoL scores and significantly greater physical disability, compared with those who did not have IA (P < .001 for both).
• IA was significantly less common among patients with , compared with those without pulmonary arterial hypertension (7.2% vs 11.3%; P = .007).

IN PRACTICE:

“Recognizing the presence of IA in SSc is an important first step, as its treatment and monitoring may alleviate some of the associated morbidity,” the researchers wrote.

SOURCE:

The lead author of the study was Eric Schwender, a medical student at the Royal College of Surgeons in Ireland, Dublin, Ireland. The study was published online in Arthritis Care & Research.

LIMITATIONS:

The inability to assess distribution and severity of IA limited the results, as did the inability to assess the impact of disease-modifying antirheumatic drugs in patients with IA.

DISCLOSURES:

The study was supported by Scleroderma Australia, Arthritis Australia, Actelion Australia, Bayer, CSL Biotherapies, GlaxoSmithKline Australia, and Pfizer, as well as grants to several researchers from the National Health and Medical Research Council of Australia. Lead author Mr. Schwender had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.